Prognostic signature

Abstract

The present disclosure relates to oropharyngeal cancer and methods, kits and systems for providing a prognosis and / or an indication of treatment response in oropharyngeal cancer.

Description

[0001] Prognostic signature

[0002] Cross-reference to related applications

[0003] The present application claims priority from Australian Provisional Patent Application No. 2024901133 filed on 22 April 2024, the contents of which are incorporated herein by reference in their entirety.

[0004] Technical Field

[0005] The present disclosure relates to oropharyngeal cancer and methods of providing a prognosis and / or an indication of treatment response in oropharyngeal cancer.

[0006] Background

[0007] The incidence of oropharyngeal cancer, and more particularly HPV-positive oropharyngeal squamous cell carcinoma, is increasing and whilst locally advanced disease has an overall highly favourable prognosis, outcomes are not uniform. The younger age at diagnosis together with persistent treatment-related toxicities has seen a worldwide collaborative effort towards treatment de-escalation attempts to reduce morbidity. Targeting the high-risk subset of patients unsuitable for de-escalation remains challenging, with the addition of clinicopathological variables of limited predictive benefit. Accordingly, there remains a need for prognostic biomarkers in oropharyngeal cancer that can be used to accurately rationalise curative-intent treatment without compromising efficacy in a cost-effective and timely manner.

[0008] Summary

[0009] The present disclosure is based on the surprising discovery of a series of proteomic signatures, which can be readily applied on pre-treatment tumour biopsies to risk stratify oropharyngeal cancer patients. By extension, each of these proteomic signatures independently demonstrate promise in classifying oropharyngeal cancer patients according to the risk of treatment failure and / or disease recurrence.

[0010] In a first aspect, the present disclosure provides a method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject. In a second aspect, the present disclosure provides a method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

[0011] In a third aspect, the present disclosure provides a method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

[0012] For the method of this aspect, the step of determining the expression level of the phosphorylated form suitably comprises determining a level or expression level of a phosphopeptide and / or a phosphosite derived from the one or more protein biomarkers.

[0013] Suitably for the above aspects, if the expression level of said one or more protein biomarkers, inclusive of a phosphorylated form thereof, is altered or modulated in the one or plurality of cancer cells, tissues or organs, the prognosis may be negative or positive.

[0014] In some examples, the above methods further include the steps of: calculating a risk score using the expression level of the one or more protein biomarkers; and comparing the risk score to a reference risk score, wherein, if (i) the risk score is equal to or higher than the reference risk score, the subject has a poor or negative prognosis, and (ii) the risk score is lower than the reference risk score, the subject has a favourable or positive prognosis.

[0015] Suitably, the prognosis derived from the methods of the above aspects is used, at least in part, to determine whether the subject would benefit from a treatment of the oropharyngeal cancer, such as chemotherapy, radiation therapy, a molecularly targeted therapy and immunotherapy.

[0016] In other examples of the above aspects, the prognosis is used, at least in part, to develop a treatment strategy for the subject. In certain examples of the above aspects, the prognosis is defined as an estimated time of survival or an estimated risk of recurrence.

[0017] In a fourth aspect, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[0018] In a fifth aspect, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[0019] In a sixth aspect, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[0020] Suitably, the step of determining the expression level of the phosphorylated form comprises determining a level or expression level of a phosphopeptide derived from the one or more protein biomarkers. In certain examples, the step of determining the expression level of the phosphorylated form comprises determining a level or expression level of a phosphosite, such as of a phosphopeptide, derived from the one or more protein biomarkers.

[0021] Suitably, the method of the fourth, fifth or sixth aspects further includes the step of administering the treatment for the oropharyngeal cancer to the subject, such as when the expression level or the level of responsiveness indicates that the treatment would be of benefit to the subject (e.g., indicates increased or at least partial responsiveness of the oropharyngeal cancer to the treatment) or more particularly, when the expression level or the level of responsiveness indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[0022] In a seventh aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[0023] In an eighth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[0024] In a ninth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of a phosphorylated form of one or more protein biomarkers has been determined in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[0025] According to particular examples of this method, the step of determining the expression level of the phosphorylated form comprises determining a level or expression level of a phosphopeptide derived from the one or more protein biomarkers. More particularly, the step of determining the expression level of the phosphorylated form suitably comprises determining a level or expression level of a phosphosite, such as of a phosphopeptide, derived from the one or more protein biomarkers.

[0026] The methods of the fourth to ninth aspects may further include the steps of: calculating a risk score using the expression level of the one or more protein biomarkers; and comparing the risk score to a reference risk score, wherein, if (i) the risk score is equal to or higher than the reference risk score, the risk score indicates that the oropharyngeal cancer is not responsive or substantially not responsive to the treatment, and (ii) the risk score is lower than the reference risk score, the risk score indicates that the oropharyngeal cancer is at least partly responsive to the treatment.

[0027] In a tenth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[0028] In an eleventh aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer. In a twelfth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[0029] According to certain examples of the present method, the step of determining the expression level of the phosphorylated form comprises determining a level or expression level of a phosphopeptide derived from the one or more protein biomarkers. In particular examples, the step of determining the expression level of the phosphorylated form comprises determining a level or expression level of a phosphosite, such as of a phosphopeptide, derived from the one or more protein biomarkers.

[0030] Referring to the methods of the fourth to twelfth aspects, the treatment suitably is or comprises one or more of chemotherapy, radiation therapy, a molecularly targeted therapy and immunotherapy.

[0031] The method of the tenth, eleventh or twelfth aspect may further include the steps of: calculating a risk score using the expression level of the one or more protein biomarkers; and comparing the risk score to a reference risk score, wherein, if (i) the risk score is equal to or higher than the reference risk score, the subject is to be administered a first treatment, and (ii) the risk score is lower than the reference risk score, the subject is to be administered a second treatment.

[0032] Suitably, the first treatment does not include chemotherapy and / or radiation therapy; and / or the second treatment includes chemotherapy and / or radiation therapy. More particularly, the second treatment suitably comprises chemotherapy and radiation therapy. In other examples, the first treatment includes a high dose of chemotherapy and / or radiation therapy; and / or the second treatment includes a low dose or a standard dose of chemotherapy and / or radiation therapy.

[0033] In a thirteenth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of one or more protein biomarkers selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof has been determined and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[0034] In a fourteenth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of one or more protein biomarkers selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof has been determined and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[0035] In a fifteenth aspect, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of a phosphorylated form of one or more protein biomarkers selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof has been determined and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[0036] In particular examples, the level of expression of the phosphorylated form has been determined at least in part by determining a level or expression level of a phosphopeptide derived from the one or more protein biomarkers. More particularly, the level of expression of the phosphorylated form has suitably been determined at least in part by determining a level or expression level of a phosphosite, such as of a phosphopeptide, derived from the one or more protein biomarkers.

[0037] Suitably, for the method of any of the thirteenth to fifteenth aspects, a risk score has been determined using the expression level of the one or more protein biomarkers, inclusive of a phosphorylated form thereof, and the risk score is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[0038] Referring to the aforementioned methods, the specificity and / or sensitivity of the method, as determined by an ROC AUC value, is at least about 0.65, at least about 0.70, at least about 0.75, at least about 0.80, at least about 0.85, at least about 0.90 or at least about 0.95. In a sixteenth aspect, the present disclosure provides a system for determining a prognosis for a subject with oropharyngeal carcinoma, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to determine the prognosis of the oropharyngeal cancer in the subject.

[0039] In a seventeenth aspect, the present disclosure provides a system for determining a prognosis for a subject with oropharyngeal carcinoma, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to determine the prognosis of the oropharyngeal cancer in the subject.

[0040] In an eighteenth aspect, the present disclosure provides a system for determining a prognosis for a subject with oropharyngeal carcinoma, the system comprising: one or more mass spectrometry units configured for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to determine the prognosis of the oropharyngeal cancer in the subject.

[0041] In a nineteenth aspect, the present disclosure provides a system for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to predict the responsiveness of the oropharyngeal cancer to the treatment.

[0042] In a twentieth aspect, the present disclosure provides a system for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to predict the responsiveness of the oropharyngeal cancer to the treatment.

[0043] In a twenty-first aspect, the present disclosure provides a system for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the system comprising: one or more mass spectrometry units configured for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to predict the responsiveness of the oropharyngeal cancer to the treatment.

[0044] In a twenty-second aspect, the present disclosure provides a kit for determining the prognosis of a subject with oropharyngeal carcinoma, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof. In a twenty-third aspect, the present disclosure provides a kit for determining the prognosis of a subject with oropharyngeal carcinoma, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof.

[0045] In a twenty-fourth aspect, the present disclosure provides a kit for determining the prognosis of a subject with oropharyngeal carcinoma, the kit comprising one or more reagents for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

[0046] In a twenty-fifth aspect, the present disclosure provides a kit for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[0047] In an twenty-sixth aspect, the present disclosure provides a kit for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof.

[0048] In a twenty-seventh aspect, the present disclosure provides a kit for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the kit comprising one or more reagents for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

[0049] Suitably for the kit of the twenty-second to twenty- seventh aspects, the one or more reagents comprise one or more probes, each probe being specific or selective for one of the one or more protein biomarkers. In some examples, each probe is independently a set of primers, a labelled nucleic acid probe, an aptamer, an antibody and / or an antibody fragment.

[0050] For the above aspects, the oropharyngeal cancer is suitably Human papillomavirus (HPV)- positive oropharyngeal squamous cell carcinoma (OPSCC).

[0051] In some examples of the above aspects, the one or more protein biomarkers comprise two or more protein biomarkers, three or more protein biomarkers, four or more protein biomarkers or five or more protein biomarkers selected from the group consisting of ACP2, AGA, BORCS6, DOK3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof. In one particular example, the one or more protein biomarkers comprise ACP2, AGA, BORCS6, DOK3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[0052] In certain examples of the above aspects, the one or more protein biomarkers comprise two or more protein biomarkers, three or more protein biomarkers, four or more protein biomarkers or five or more protein biomarkers selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH. For some examples, the one or more protein biomarkers comprise ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[0053] In some examples of the above aspects, the one or more protein biomarkers comprise two or more protein biomarkers, three or more protein biomarkers, four or more protein biomarkers or five or more protein biomarkers selected from the group consisting of ALDOA, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, PSMB4 and SPRR3, or a fragment, variant or derivative thereof. In one particular example, the one or more protein biomarkers comprise ALDOA, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, PSMB4 and SPRR3, or a fragment, variant or derivative thereof. In some examples of the above aspects, the one or more protein biomarkers comprise two or more protein biomarkers, three or more protein biomarkers, four or more protein biomarkers or five or more protein biomarkers selected from the group consisting of AGRN, ALDO A, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof. In one particular example, the one or more protein biomarkers comprise AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof.

[0054] In various examples of the above aspects, the one or more protein biomarkers comprise two or more protein biomarkers, three or more protein biomarkers, four or more protein biomarkers or five or more protein biomarkers selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1- 6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof. In one particular example, the one or more protein biomarkers comprise ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

[0055] Suitably, the system of the sixteenth to twenty-first aspects or the kit of the twenty-second to twenty-seventh aspects are suitable for use in the method of one or more of the first to fifteenth aspects.

[0056] Brief description of the drawings

[0057] The following figures form part of the present specification and are included to further demonstrate certain aspects of the present disclosure. The disclosure may be better understood by reference to one or more of these figures in combination with the detailed description of specific embodiments presented herein. It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[0058] Figure 1. (a) Summary of samples included in Example 1. (b) Summary of the proteomic workflow utilised for Example 1. In brief, tumour core and normal adjacent tissue (NAT) samples underwent high pressure and temperature for lysis and digestion of proteins to peptides by trypsin / LysC. Samples were analysed in duplicate via DIA-MS in two separate instruments. Proteomic data was processed using DIA-NN software and quantitative data on peptides was obtained. Protein abundance was inferred and single peptide proteins (SiPPs) present in >20% of the samples were included in the downstream analyses.

[0059] Figure 2. Overview of DIA-MS data set and 26-peptide signature: a) Overview of DIA-MS data set. Number of peptides and proteins identified using DIA-MS samples from all 124 patients (‘All’ includes both tumour and normal adjacent tissues (NAT)) and only in the tumour subset of samples. The number of peptides is shown in each filtering step with 405 being associated with recurrence-free survival (RFS) (q-value <0.05) and used to obtain the prognostic signature. The concordance index (C-Index) of the (differentially abundant peptide (DAPep) signature from multivariate Cox modelling was 0.947. RFS: recurrence-free survival; Peptide intensity filtering was applied (peptides with <15 raw intensity value were discarded), b) List of 26-proteins identified by the 26-peptide signature (amino acid sequence, predicted gene name) with hazard ratio (HR, with 95% confidence intervals (CI)) and p-values in multivariate model, ranked according to their significance from top to bottom. The signature was identified by Lasso- regularized multivariate Cox proportional hazard model as input to a multivariate Cox model with forward feature selection algorithm and has a C-index of 0.947. The squares and intervals in the plot represent the values of hazard ratios and Cis, respectively.

[0060] Figure 3. Differential abundance of 233 unique protein groups identified from 405 Differentially Abundant Peptides (DAPeps) discriminates recurrence from non-recurrence: a) Volcano plot shows the distribution of 233 proteins significantly up- or down-regulated in the recurrence (R) relative to the non-recurrence (NR) in HPV-positive-associated OPSCC (HPV+OPSCC) patient samples. There were 87 peptides (from 52 unique protein groups) down-regulated in R vs NR and 318 peptides (from 181 unique protein groups) up-regulated in R at an adjusted p- value of 0.01 (1% FDR). Axes show fold-change (FC) > 1.5 adjusted p-value < 0.01. Significant peptides are indicated in red (increased in R) or blue colour (decreased in R). Most peptides showed low FC after differential expression analysis (coloured grey), b) Heatmap representation of the z-scores obtained after unsupervised hierarchical clustering of the differentially abundant peptides from panel a). Expression data are converted to z-scores. Samples are shown on the x- axis whereas peptides are clustered on the y-axis against RFS or some clinicopathological variables.

[0061] Figure 4. A 26-peptide signature stratifies HPV+ OPSCC patients into three risk groups for recurrence free survival (RFS) or overall survival (OS): Kaplan-Meier (KM) curves with 95% Cis based on the 26-peptide risk score stratification of HPV+ OPSCC patients. The signatures were separated into low-, intermediate- and high-risk groups for a) recurrence free survival (RFS) or b) overall survival (OS) based on the median cut-off, and the respective numbers of samples in each risk group are shown. Log rank test was used to assess the p-value of the differences between the KM curves. The signatures were built using the coefficients from the training dataset. The shaded area around each curve represents 95% confidence interval. The dotted lines mark median probabilities.

[0062] Figure 5. Multivariate cox regression model and ROC curves incorporating the 26-peptide risk score: a) Forest plot showing important clinicopathological variables along with risk score and their association with disease specific survival using a multivariate Cox regression model. Mean hazard ratios are shown as squares and whiskers represent 95 % confidence intervals (CI), b) Receiver operating characteristic curve (ROC) curve at 5 years after the date of treatment for the 26-peptide risk score. The predicted area under the ROC Curve (AUC) 5-years is shown comparing the proteomic risk score with 6 clinicopathological variables.

[0063] Figure 6. Differential abundance 1,614 unique protein groups from 4.834 DAPeps discriminates tumour and NAT patient samples, a) Volcano plot shows the distribution of 1,614 proteins significantly up- or down-regulated in recurrence (R) relative to the non-recurrence (NR) in HPV- associated OPSCC patient samples. There were 2,018 peptides (from 396 unique protein groups) down-regulated in Tumor vs NAT and 2,816 peptides (from 1,218 unique protein groups) up-regulated in Tumor at an adjusted p-value of 0.01 (1% FDR). Axes show fold-change (FC) > 1.5 adjusted p-value < 0.01. Significant peptides are indicated in red (increased in R) or blue colour (decreased in R). Most peptides showed low FC after differential expression analysis (coloured grey), b) Heatmap representation of the z-scores obtained after unsupervised hierarchical clustering of the DAPeps from panel a). Expression data are converted to z-scores. Samples are shown on the x-axis whereas peptides are clustered on the y-axis against tumour vs NAT samples or some clinicopathological variables.

[0064] Figure 7. Top 15 cellular functions and pathways for DAPeps in tumour vs to NAT samples. Impacted pathways were analysed separately for the a) up-regulated or b) down-regulated proteins associated with the DAPeps according to the number of proteins in that function (# genes) and coloured according to the adjusted p-value. Pathways were identified for 2,816 peptides (1,218 unique proteins) up-regulated in tumor or 2,018 peptides (396 proteins) down-regulated in tumor. Pathways up-regulated in the tumors include 971 GO Biological Processes, 83 KEGG Pathways and 413 Reactome Pathways, and those down-regulated include 428 GO Biological Processes, 24 KEGG Pathways and 93 Reactome Pathways.

[0065] Figure 8. Distribution of the quantified peptides or proteins among the number of patient tumour samples. The distribution of (a) 34,898 quantified peptides or (b) 5,199 identified tumour proteins among all patient tumour samples. Graphs show the number of peptides or proteins detected and quantified against the number of MS runs in which they were identified (all MS runs were in duplicate, where the duplicates were run on different instruments). For proteins among the list 5,199 tumour proteins their identifications were derived from either 2 or more peptides per protein, or 1,189 of them were single peptide proteins (SiPPs, a further 344 SiPPs were removed from down-stream analysis if they were detected in <20% of tumour samples). Overall, most peptides and proteins were detected in most of the samples.

[0066] Figure 9. Top 15 cellular functions and pathways for DAPep tumor samples from recurrence vs non-recurrence. Impacted pathways were analysed separately for the a) up-regulated or b) down-regulated proteins associated with the DAPeps according to the number of proteins in that function (# genes) and coloured according to the adjusted p-value. Pathways were identified for 318 peptides (181 unique proteins) up-regulated in recurrence (R) or 87 peptides (52 proteins) down-regulated in R. Pathways up-regulated in the R group included 227 GO Biological Processes, 8 KEGG Pathways and 12 Reactome Pathways, and those down-regulated included 83 GO Biological Processes, 5 KEGG Pathways and 23 Reactome Pathways.

[0067] Figure 10. Overview of DIA-MS data set for 20-protein signature. Number of peptides and proteins identified using DIA-MS samples from all 124 patients (‘All’ includes both tumour and normal adjacent tissues (NAT)) and only in the patient tumour subset of samples. The number of proteins is shown in each filtering step with 255 being associated with RFS (q-value <0.05) and used to obtain the prognostic signature. The concordance index (C -Index) of the 20-protein signature from multivariate Cox modelling was 0.897. RFS: recurrence-free survival; Peptide intensity fdtering was applied (peptides with <15 raw intensity value were discarded).

[0068] Figure 11. Differential abundance of 255 unique protein groups identified from 5,191 differentially abundant proteins (DAProts) discriminates recurrence from non-recurrence. a) Volcano plot shows the distribution of 255 proteins significantly up- or down-regulated in the recurrence (R) relative to the non- recurrence (NR) in HPV+OPSCC patient samples. There were 42 unique protein groups down-regulated in R vs NR and 213 unique protein groups up-regulated in R at an adjusted p-value of 0.01 (1% FDR). Axes show fold-change (FC) > 1.5 adjusted p-value < 0.01. Significant proteins are indicated in red (increased in R) or blue colour (decreased in R). Most proteins showed low FC after differential expression analysis (coloured grey), b) Heatmap representation of the z-scores obtained after unsupervised hierarchical clustering of the differentially abundant proteins from panel a). Expression data are converted to z-scores. Samples are shown on the x-axis whereas proteins are clustered on the y-axis against RFS or selected clinicopathological variables. Figure 12. Top 15 cellular functions and pathways for DAProt tumor samples from recurrence (responders) vs non-recurrence (non-responders). Impacted pathways were analysed separately for the a) up-regulated or b) down-regulated proteins associated with the DAPeps according to the number of proteins in that function (# genes) and coloured according to the adjusted p-value. Pathways were identified for 213 unique up-regulated proteins in recurrence / responders (R) or 42 proteins) down-regulated in R.

[0069] Figure 13. Overview of the 20-protein signature, a) List of 20-protein signature (predictor) with hazard ratio (with 95% confidence intervals (CI)) and p-values in multivariate model, ranked according to their significance from top to bottom. The signature, with C-index = 00.897, was identified by Lasso-regularized multivariate Cox proportional hazard model being used as an input to a multivariate Cox model with forward feature selection algorithm. The squares and intervals in the plot represent the values of hazard ratios and Cis, respectively, b) Overlap between signatures. Two proteins (STAG1 / Q8WVM7 and ETHE1 / O95571) overlap between the peptides that comprise the 20-protein signature and the 26-peptide signature.

[0070] Figure 14. A 20-protein signature stratifies HPV+OPSCC patients into three risk groups for recurrence free survival (RFS) or overall survival (OS). Kaplan-Meier (KM) curves with 95% Cis based on the 20-protein risk score stratification of HPV+ OPSCC patients. The risk scores were dichotomized into low, intermediate and high risk groups for a) recurrence free survival (RFS) or b) overall survival (OS) based on the median cut-off, and shown are the respective numbers of samples corresponding to each risk group. Log rank test was used to measure the differences between the KM curves as p-value. The risk scores were built using the coefficients from the training dataset. The shaded area around each curve represents 95% confidence interval. The dotted lines mark median probabilities.

[0071] Figure 15. Multivariate cox regression model and ROC curves incorporating the 20-protein risk score, a) Forest plot showing important clinicopathological variables along with risk score and their association with disease specific survival using a multivariate Cox regression model. Mean hazard ratios are shown as squares and whiskers represent 95 % confidence intervals (CI), b) ROC curve at 5 years after the date of treatment for the 20-protein risk score. The predicted AUC 5-years is shown comparing the proteomic risk score with 6 clinicopathological variables. Figure 16. Schematic of workflow for phosphopeptide analysis.

[0072] Figure 17. Principal component analysis of phosphopeptides.

[0073] Figure 18. Results of STRING analysis for differentially abundant phosphopeptides (DAPhos) in tumour tissue.

[0074] Figure 19. Results of STRING analysis for differentially abundant phosphopeptides (DAPhos) in adjacent normal (non-tumour) tissue. Figure 20. Hazard ratios (95% CI) with their significance for DAPhos for top significant covariates.

[0075] Figure 21. Hazard ratios (95% CI) with their significance for DAPhos for least significant covariates. Figure 22. Kaplan-Meier curve of recurrence-free survival for a CDKN2A phosphopeptide.

[0076] Figure 23. Kaplan-Meier curve of recurrence-free survival after 10 years for the 26- phosphopeptides identified as having upregulated or down regulated expression showing stratification of HPV+OPSCC patients into low, intermediate and high risk groups.

[0077] Figure 24. Kaplan-Meier curve of overall survival for the 26-phosphopeptides identified as having upregulated or down regulated expression showing stratification of HPV+OPSCC patients into low, intermediate and high risk groups.

[0078] Key to the Sequence Listing

[0079] SEQ ID NO: 1 Amino acid sequence of ACP2

[0080] SEQ ID NO: 2 Amino acid sequence of AGA

[0081] SEQ ID NO: 3 Amino acid sequence of BORCS6

[0082] SEQ ID NO: 4 Amino acid sequence of COL8A1

[0083] SEQ ID NO: 5 Amino acid sequence of DOK3

[0084] SEQ ID NO: 6 Amino acid sequence of ETHE 1

[0085] SEQ ID NO: 7 Amino acid sequence of FNBP1

[0086] SEQ ID NO: 8 Amino acid sequence of GOLGA3

[0087] SEQ ID NO: 9 Amino acid sequence of GSTO1

[0088] SEQ ID NO: 10 Amino acid sequence of HAPLN3

[0089] SEQ ID NO: 11 Amino acid sequence of HLA-DPA1

[0090] SEQ ID NO: 12 Amino acid sequence of HLA-DRB4

[0091] SEQ ID NO: 13 Amino acid sequence of IGHM

[0092] SEQ ID NO: 14 Amino acid sequence of ITIH2

[0093] SEQ ID NO: 15 Amino acid sequence of IVL

[0094] SEQ ID NO: 16 Amino acid sequence of MGST2

[0095] SEQ ID NO: 17 Amino acid sequence of PSMG1

[0096] SEQ ID NO: 18 Amino acid sequence of STAG1

[0097] SEQ ID NO: 19 Amino acid sequence of TAP2

[0098] SEQ ID NO: 20 Amino acid sequence of UGDH

[0099] SEQ ID NO: 21 Amino acid sequence of AGRN

[0100] SEQ ID NO: 22 Amino acid sequence of ALDOA

[0101] SEQ ID NO: 23 Amino acid sequence of ARL6IP5 SEQ ID NO: 24 Amino acid sequence of ATP2A2

[0102] SEQ ID NO: 25 Amino acid sequence of CDS2

[0103] SEQ ID NO: 26 Amino acid sequence of CNDP2

[0104] SEQ ID NO: 27 Amino acid sequence of CTSZ

[0105] SEQ ID NO: 28 Amino acid sequence of DECRl

[0106] SEQ ID NO: 29 Amino acid sequence of ERP29

[0107] SEQ ID NO: 30 Amino acid sequence of GAPVD1

[0108] SEQ ID NO: 31 Amino acid sequence of GARS1

[0109] SEQ ID NO: 32 Amino acid sequence of HLA-A

[0110] SEQ ID NO: 33 Amino acid sequence of KRT17

[0111] SEQ ID NO: 34 Amino acid sequence of LAP3

[0112] SEQ ID NO: 35 Amino acid sequence of LMNBl

[0113] SEQ ID NO: 36 Amino acid sequence of MMP2

[0114] SEQ ID NO: 37 Amino acid sequence of MVP

[0115] SEQ ID NO: 38 Amino acid sequence of NOP56

[0116] SEQ ID NO: 39 Amino acid sequence of OPA3

[0117] SEQ ID NO: 40 Amino acid sequence of PSMB4

[0118] SEQ ID NO: 41 Amino acid sequence of S 100A4

[0119] SEQ ID NO: 42 Amino acid sequence of SPRR3

[0120] SEQ ID NO: 43 Amino acid sequence of TCEAl

[0121] SEQ ID NO: 44 Amino acid sequence of WDR81

[0122] SEQ ID NO: 45 Amino acid sequence of ACP2_35-41

[0123] SEQ ID NO: 46 Amino acid sequence of ACP2_71-84

[0124] SEQ ID NO: 47 Amino acid sequence of ACP2_110-129

[0125] SEQ ID NO: 48 Amino acid sequence of ACP2_171-181

[0126] SEQ ID NO: 49 Amino acid sequence of ACP2_220-231

[0127] SEQ ID NO: 50 Amino acid sequence of ACP2_255-265

[0128] SEQ ID NO: 51 Amino acid sequence of ACP2_349-356

[0129] SEQ ID NO: 52 Amino acid sequence of ACP2_357-364

[0130] SEQ ID NO: 53 Amino acid sequence of AGA_170-177

[0131] SEQ ID NO: 54 Amino acid sequence of AGA_266-277

[0132] SEQ ID NO: 55 Amino acid sequence of BORCS6_6-31

[0133] SEQ ID NO: 56 Amino acid sequence of BORCS6_32-41

[0134] SEQ ID NO: 57 Amino acid sequence of BORCS6_76-94

[0135] SEQ ID NO: 58 Amino acid sequence of BORCS6_195-209

[0136] SEQ ID NO: 59 Amino acid sequence of BORCS6_331-340 SEQ ID NO: 60 Amino acid sequence of BORCS6_348-357

[0137] SEQ ID NO: 61 Amino acid sequence of COL8A1_110-117

[0138] SEQ ID NO: 62 Amino acid sequence of COL8A1_671-680

[0139] SEQ ID NO: 63 Amino acid sequence of DOK3_130-146

[0140] SEQ ID NO: 64 Amino acid sequence of DOK3_147-158

[0141] SEQ ID NO: 65 Amino acid sequence of DOK3_234-248

[0142] SEQ ID NO: 66 Amino acid sequence of DOK3_314-327

[0143] SEQ ID NO: 67 Amino acid sequence of DOK3_328-341

[0144] SEQ ID NO: 68 Amino acid sequence of ETHEl_17-26

[0145] SEQ ID NO: 69 Amino acid sequence of ETHEl_27-43

[0146] SEQ ID NO: 70 Amino acid sequence of ETHE1_47-6O

[0147] SEQ ID NO: 71 Amino acid sequence of ETHEl_72-92

[0148] SEQ ID NO: 72 Amino acid sequence of ETHE1_93-1O4

[0149] SEQ ID NO: 73 Amino acid sequence of ETHE1_1O5-121

[0150] SEQ ID NO: 74 Amino acid sequence of ETHE1_122-13O

[0151] SEQ ID NO: 75 Amino acid sequence of ETHE1_131-159

[0152] SEQ ID NO: 76 Amino acid sequence of ETHE1_164-172

[0153] SEQ ID NO: 77 Amino acid sequence of ETHE1_182-2O9

[0154] SEQ ID NO: 78 Amino acid sequence of ETHEl_215-224

[0155] SEQ ID NO: 79 Amino acid sequence of FNBPl_36-44

[0156] SEQ ID NO: 80 Amino acid sequence of FNBP1_158-166

[0157] SEQ ID NO: 81 Amino acid sequence of FNBP1_188-196

[0158] SEQ ID NO: 82 Amino acid sequence of FNBPl_216-222

[0159] SEQ ID NO: 83 Amino acid sequence of FNBPl_233-239

[0160] SEQ ID NO: 84 Amino acid sequence of FNBPl_240-247

[0161] SEQ ID NO: 85 Amino acid sequence of FNBPl_263-273

[0162] SEQ ID NO: 86 Amino acid sequence of FNBPl_458-467

[0163] SEQ ID NO: 87 Amino acid sequence of FNBPl_475-485

[0164] SEQ ID NO: 88 Amino acid sequence of FNBPl_534-556

[0165] SEQ ID NO: 89 Amino acid sequence of FNBP1_594-612

[0166] SEQ ID NO: 90 Amino acid sequence of GOLGA3_754-764

[0167] SEQ ID NO: 91 Amino acid sequence of GOLGA3_776-786

[0168] SEQ ID NO: 92 Amino acid sequence of GOLGA3_1018-1028

[0169] SEQ ID NO: 93 Amino acid sequence of GOLGA3_1029-1043

[0170] SEQ ID NO: 94 Amino acid sequence of GST01_12-25

[0171] SEQ ID NO: 95 Amino acid sequence of GST01_31-37 SEQ ID NO: 96 Amino acid sequence of GST01_49-57

[0172] SEQ ID NO: 97 Amino acid sequence of GST01_102-110

[0173] SEQ ID NO: 98 Amino acid sequence of GSTO1_115-122

[0174] SEQ ID NO: 99 Amino acid sequence of GSTO1_123-132

[0175] SEQ ID NO: 100 Amino acid sequence of GSTOl_153-160

[0176] SEQ ID NO: 101 Amino acid sequence of GSTOl_201-207

[0177] SEQ ID NO: 102 Amino acid sequence of GST01_208-220

[0178] SEQ ID NO: 103 Amino acid sequence of HAPLN3_74-82

[0179] SEQ ID NO: 104 Amino acid sequence of HAPLN3_1OO-1O8

[0180] SEQ ID NO: 105 Amino acid sequence of HAPLN3_111-118

[0181] SEQ ID NO: 106 Amino acid sequence of HAPLN3_165-176

[0182] SEQ ID NO: 107 Amino acid sequence of HAPLN3_231-243

[0183] SEQ ID NO: 108 Amino acid sequence of HAPLN3_341-350

[0184] SEQ ID NO: 109 Amino acid sequence of HLA-DPAl_34-48

[0185] SEQ ID NO: 110 Amino acid sequence of HLA-DPA1_172-178

[0186] SEQ ID NO: 111 Amino acid sequence of HLA-DPA1_ 196-207

[0187] SEQ ID NO: 112 Amino acid sequence of HLA-DRB4_59-68

[0188] SEQ ID NO: 113 Amino acid sequence of HLA-DRB4_102-109

[0189] SEQ ID NO: 114 Amino acid sequence of HLA-DRB4_110-122

[0190] SEQ ID NO: 115 Amino acid sequence of IGHM_65-76

[0191] SEQ ID NO: 116 Amino acid sequence of IGHM_ 100-112

[0192] SEQ ID NO: 117 Amino acid sequence of IGHM_113-120

[0193] SEQ ID NO: 118 Amino acid sequence of IGHM_121-128

[0194] SEQ ID NO: 119 Amino acid sequence of IGHM_132-142

[0195] SEQ ID NO: 120 Amino acid sequence of IGHM_143-150

[0196] SEQ ID NO: 121 Amino acid sequence of IGHM_154-169

[0197] SEQ ID NO: 122 Amino acid sequence of IGHM_170-177

[0198] SEQ ID NO: 123 Amino acid sequence of IGHM_178-185

[0199] SEQ ID NO: 124 Amino acid sequence of IGHM_224-238

[0200] SEQ ID NO: 125 Amino acid sequence of IGHM_301-315

[0201] SEQ ID NO: 126 Amino acid sequence of IGHM_316-322

[0202] SEQ ID NO: 127 Amino acid sequence of IGHM_323-338

[0203] SEQ ID NO: 128 Amino acid sequence of IGHM_345-368

[0204] SEQ ID NO: 129 Amino acid sequence of IGHM_369-376

[0205] SEQ ID NO: 130 Amino acid sequence of IGHM_377-391

[0206] SEQ ID NO: 131 Amino acid sequence of IGHM_377-391 SEQ ID NO: 132 Amino acid sequence of ITIH2_77-84

[0207] SEQ ID NO: 133 Amino acid sequence of ITIH2_85-93

[0208] SEQ ID NO: 134 Amino acid sequence of ITIH2_94-112

[0209] SEQ ID NO: 135 Amino acid sequence of ITIH2_157-166

[0210] SEQ ID NO: 136 Amino acid sequence of ITIH2_167-176

[0211] SEQ ID NO: 137 Amino acid sequence of ITIH2_177-187

[0212] SEQ ID NO: 138 Amino acid sequence of ITIH2_ 198-204

[0213] SEQ ID NO: 139 Amino acid sequence of ITIH2_208-222

[0214] SEQ ID NO: 140 Amino acid sequence of ITIH2_223-242

[0215] SEQ ID NO: 141 Amino acid sequence of ITIH2_247-259

[0216] SEQ ID NO: 142 Amino acid sequence of ITIH2_266-280

[0217] SEQ ID NO: 143 Amino acid sequence of ITIH2_335-341

[0218] SEQ ID NO: 144 Amino acid sequence of ITIH2_342-356

[0219] SEQ ID NO: 145 Amino acid sequence of ITIH2_360-367

[0220] SEQ ID NO: 146 Amino acid sequence of ITIH2_380-394

[0221] SEQ ID NO: 147 Amino acid sequence of ITIH2_465-475

[0222] SEQ ID NO: 148 Amino acid sequence of ITIH2_476-487

[0223] SEQ ID NO: 149 Amino acid sequence of ITIH2_489-499

[0224] SEQ ID NO: 150 Amino acid sequence of ITIH2_574-581

[0225] SEQ ID NO: 151 Amino acid sequence of ITIH2_582-596

[0226] SEQ ID NO: 152 Amino acid sequence of ITIH2_583-596

[0227] SEQ ID NO: 153 Amino acid sequence of ITIH2_597-605

[0228] SEQ ID NO: 154 Amino acid sequence of ITIH2_611-638

[0229] SEQ ID NO: 155 Amino acid sequence of IVL_22-35

[0230] SEQ ID NO: 156 Amino acid sequence of IVL_47-58

[0231] SEQ ID NO: 157 Amino acid sequence of IVL_47-62

[0232] SEQ ID NO: 158 Amino acid sequence of IVL_69-80

[0233] SEQ ID NO: 159 Amino acid sequence of IVL_128-140

[0234] SEQ ID NO: 160 Amino acid sequence of IVL_129-140

[0235] SEQ ID NO: 161 Amino acid sequence of IVL_129-141

[0236] SEQ ID NO: 162 Amino acid sequence of IVL_142-148

[0237] SEQ ID NO: 163 Amino acid sequence of IVL_149-164

[0238] SEQ ID NO: 164 Amino acid sequence of IVL_150-164

[0239] SEQ ID NO: 165 Amino acid sequence of IVL_165-174

[0240] SEQ ID NO: 166 Amino acid sequence of IVL_265-284

[0241] SEQ ID NO: 167 Amino acid sequence of IVL_285-294 SEQ ID NO 168 Amino acid sequence of IVL_302-314

[0242] SEQ ID NO 169 Amino acid sequence of IVL_315-324

[0243] SEQ ID NO 170 Amino acid sequence of IVL_385-394

[0244] SEQ ID NO 171 Amino acid sequence of IVL_395-404

[0245] SEQ ID NO 172 Amino acid sequence of IVL_405-418

[0246] SEQ ID NO 173 Amino acid sequence of IVL_419-431

[0247] SEQ ID NO 174 Amino acid sequence of IVL_432-441

[0248] SEQ ID NO 175 Amino acid sequence of IVL_442-461

[0249] SEQ ID NO 176 Amino acid sequence of IVL_469-481

[0250] SEQ ID NO 177 Amino acid sequence of IVL_486-501

[0251] SEQ ID NO 178 Amino acid sequence of IVL_509-521

[0252] SEQ ID NO 179 Amino acid sequence of IVL_538-562

[0253] SEQ ID NO 180 Amino acid sequence of IVL_563-575

[0254] SEQ ID NO 181 Amino acid sequence of MGST2_35-48

[0255] SEQ ID NO 182 Amino acid sequence of PSMGl_16-29

[0256] SEQ ID NO 183 Amino acid sequence of PSMG1_161-170

[0257] SEQ ID NO 184 Amino acid sequence of PSMG1_177-19O

[0258] SEQ ID NO 185 Amino acid sequence of STAG 1_141-149

[0259] SEQ ID NO 186 Amino acid sequence of STAGl_659-668

[0260] SEQ ID NO 187 Amino acid sequence of STAGl_1038-1049

[0261] SEQ ID NO 188 Amino acid sequence of STAG l_1039- 1049

[0262] SEQ ID NO 189 Amino acid sequence of STAG l_1050- 1060

[0263] SEQ ID NO 190 Amino acid sequence of STAG1_1102-1123

[0264] SEQ ID NO 191 Amino acid sequence of STAG 1_1188-1206

[0265] SEQ ID NO 192 Amino acid sequence of TAP2_211-220

[0266] SEQ ID NO 193 Amino acid sequence of TAP2_225-235

[0267] SEQ ID NO 194 Amino acid sequence of TAP2_227-235

[0268] SEQ ID NO 195 Amino acid sequence of TAP2_236-245

[0269] SEQ ID NO 196 Amino acid sequence of TAP2_320-327

[0270] SEQ ID NO 197 Amino acid sequence of TAP2_334-343

[0271] SEQ ID NO 198 Amino acid sequence of TAP2_344-354

[0272] SEQ ID NO 199 Amino acid sequence of TAP2_355-363

[0273] SEQ ID NO 200 Amino acid sequence of TAP2_443-449

[0274] SEQ ID NO 201 Amino acid sequence of TAP2_450-469

[0275] SEQ ID NO 202 Amino acid sequence of TAP2_562-575

[0276] SEQ ID NO 203 Amino acid sequence of TAP2_576-603 SEQ ID NO: 204 Amino acid sequence of TAP2_627-651

[0277] SEQ ID NO: 205 Amino acid sequence of TAP2_669-679

[0278] SEQ ID NO: 206 Amino acid sequence of UGDH_32-41

[0279] SEQ ID NO: 207 Amino acid sequence of UGDH_42-58

[0280] SEQ ID NO: 208 Amino acid sequence of UGDH_68-80

[0281] SEQ ID NO: 209 Amino acid sequence of UGDH_81-94

[0282] SEQ ID NO: 210 Amino acid sequence of UGDH_116-124

[0283] SEQ ID NO: 211 Amino acid sequence of UGDH_178-190

[0284] SEQ ID NO: 212 Amino acid sequence of UGDH_208-220

[0285] SEQ ID NO: 213 Amino acid sequence of UGDH_221-230

[0286] SEQ ID NO: 214 Amino acid sequence of UGDH_231-260

[0287] SEQ ID NO: 215 Amino acid sequence of UGDH_280-298

[0288] SEQ ID NO: 216 Amino acid sequence of UGDH_299-311

[0289] SEQ ID NO: 217 Amino acid sequence of UGDH_318-329

[0290] SEQ ID NO: 218 Amino acid sequence of UGDH_318-330

[0291] SEQ ID NO: 219 Amino acid sequence of UGDH_331-339

[0292] SEQ ID NO: 220 Amino acid sequence of UGDH_347-355

[0293] SEQ ID NO: 221 Amino acid sequence of UGDH_374-393

[0294] SEQ ID NO: 222 Amino acid sequence of UGDH_444-464

[0295] SEQ ID NO: 223 Amino acid sequence of UGDH_471-481

[0296] SEQ ID NO: 224 Amino acid sequence of AGRN_83-91

[0297] SEQ ID NO: 225 Amino acid sequence of AGRN_92-113

[0298] SEQ ID NO: 226 Amino acid sequence of AGRN_114-129

[0299] SEQ ID NO: 227 Amino acid sequence of AGRN_401-408

[0300] SEQ ID NO: 228 Amino acid sequence of AGRN_419-434

[0301] SEQ ID NO: 229 Amino acid sequence of AGRN_435-442

[0302] SEQ ID NO: 230 Amino acid sequence of AGRN_542-552

[0303] SEQ ID NO: 231 Amino acid sequence of AGRN_647-660

[0304] SEQ ID NO: 232 Amino acid sequence of AGRN_741-751

[0305] SEQ ID NO: 233 Amino acid sequence of AGRN_1159-1167

[0306] SEQ ID NO: 234 Amino acid sequence of AGRN_1168-1178

[0307] SEQ ID NO: 235 Amino acid sequence of AGRN_1202-1215

[0308] SEQ ID NO: 236 Amino acid sequence of AGRN_1279-1287

[0309] SEQ ID NO: 237 Amino acid sequence of AGRN_1369-1380

[0310] SEQ ID NO: 238 Amino acid sequence of AGRN_1381-1389

[0311] SEQ ID NO: 239 Amino acid sequence of AGRN_1402-1416 SEQ ID NO: 240 Amino acid sequence of AGRN_1417-1429

[0312] SEQ ID NO: 241 Amino acid sequence of AGRN_1419-1429

[0313] SEQ ID NO: 242 Amino acid sequence of AGRN_1434-1456

[0314] SEQ ID NO: 243 Amino acid sequence of AGRN_1510-1517

[0315] SEQ ID NO: 244 Amino acid sequence of AGRN_1522-1529

[0316] SEQ ID NO: 245 Amino acid sequence of AGRN_1530-1541

[0317] SEQ ID NO: 246 Amino acid sequence of AGRN_ 1662- 1671

[0318] SEQ ID NO: 247 Amino acid sequence of AGRN_1672-1683

[0319] SEQ ID NO: 248 Amino acid sequence of AGRN_1688-1696

[0320] SEQ ID NO: 249 Amino acid sequence of AGRN_1715-1726

[0321] SEQ ID NO: 250 Amino acid sequence of AGRN_1717-1726

[0322] SEQ ID NO: 251 Amino acid sequence of AGRN_1765-1777

[0323] SEQ ID NO: 252 Amino acid sequence of AGRN_1781-1800

[0324] SEQ ID NO: 253 Amino acid sequence of AGRN_18O1-181O

[0325] SEQ ID NO: 254 Amino acid sequence of AGRN_1811-1824

[0326] SEQ ID NO: 255 Amino acid sequence of AGRN_1910-1921

[0327] SEQ ID NO: 256 Amino acid sequence of AGRN_ 1966- 1974

[0328] SEQ ID NO: 257 Amino acid sequence of ALDOA_14-22

[0329] SEQ ID NO: 258 Amino acid sequence of ALDOA_15-22

[0330] SEQ ID NO: 259 Amino acid sequence of ALDOA_23-42

[0331] SEQ ID NO: 260 Amino acid sequence of ALDOA_29-42

[0332] SEQ ID NO: 261 Amino acid sequence of ALDOA_29-43

[0333] SEQ ID NO: 262 Amino acid sequence of ALDOA_43-56

[0334] SEQ ID NO: 263 Amino acid sequence of ALDOA_44-56

[0335] SEQ ID NO: 264 Amino acid sequence of ALDOA_44-57

[0336] SEQ ID NO: 265 Amino acid sequence of ALDO A_61-69

[0337] SEQ ID NO: 266 Amino acid sequence of ALDO A_61-87

[0338] SEQ ID NO: 267 Amino acid sequence of ALDOA_70-87

[0339] SEQ ID NO: 268 Amino acid sequence of ALDOA_88-99

[0340] SEQ ID NO: 269 Amino acid sequence of ALDOA_93-99

[0341] SEQ ID NO: 270 Amino acid sequence of ALDO A_100- 108

[0342] SEQ ID NO: 271 Amino acid sequence of ALDOA_109-134

[0343] SEQ ID NO: 272 Amino acid sequence of ALDOA_112-134

[0344] SEQ ID NO: 273 Amino acid sequence of ALDO A_150- 173

[0345] SEQ ID NO: 274 Amino acid sequence of ALDO A_154- 173

[0346] SEQ ID NO: 275 Amino acid sequence of ALDOA_244-258 SEQ ID NO: 276 Amino acid sequence of ALDOA_244-259

[0347] SEQ ID NO: 277 Amino acid sequence of ALDOA_260-289

[0348] SEQ ID NO: 278 Amino acid sequence of ALDOA_290-304

[0349] SEQ ID NO: 279 Amino acid sequence of ALDOA_305-312

[0350] SEQ ID NO: 280 Amino acid sequence of ALDOA_323-330

[0351] SEQ ID NO: 281 Amino acid sequence of ALDOA_323-331

[0352] SEQ ID NO: 282 Amino acid sequence of ALDOA_331-342

[0353] SEQ ID NO: 283 Amino acid sequence of ALDOA_332-342

[0354] SEQ ID NO: 284 Amino acid sequence of ALDOA_343-364

[0355] SEQ ID NO: 285 Amino acid sequence of ARL6IP5_10-20

[0356] SEQ ID NO: 286 Amino acid sequence of ARL6IP5_159-178

[0357] SEQ ID NO: 287 Amino acid sequence of ARL6IP5_160-178

[0358] SEQ ID NO: 288 Amino acid sequence of ARL6IP5_179-185

[0359] SEQ ID NO: 289 Amino acid sequence of ATP2A2_8-30

[0360] SEQ ID NO: 290 Amino acid sequence of ATP2A2_144-158

[0361] SEQ ID NO: 291 Amino acid sequence of ATP2A2_144-164

[0362] SEQ ID NO: 292 Amino acid sequence of ATP2A2_190-198

[0363] SEQ ID NO: 293 Amino acid sequence of ATP2A2_219-234

[0364] SEQ ID NO: 294 Amino acid sequence of ATP2A2_235-246

[0365] SEQ ID NO: 295 Amino acid sequence of ATP2A2_237-246

[0366] SEQ ID NO: 296 Amino acid sequence of ATP2A2_372-397

[0367] SEQ ID NO: 297 Amino acid sequence of ATP2A2_452-460

[0368] SEQ ID NO: 298 Amino acid sequence of ATP2A2_468-476

[0369] SEQ ID NO: 299 Amino acid sequence of ATP2A2_493-505

[0370] SEQ ID NO: 300 Amino acid sequence of ATP2A2_529-541

[0371] SEQ ID NO: 301 Amino acid sequence of ATP2A2_534-541

[0372] SEQ ID NO: 302 Amino acid sequence of ATP2A2_550-559

[0373] SEQ ID NO: 303 Amino acid sequence of ATP2A2_560-571

[0374] SEQ ID NO: 304 Amino acid sequence of ATP2A2_560-572

[0375] SEQ ID NO: 305 Amino acid sequence of ATP2A2_573-585

[0376] SEQ ID NO: 306 Amino acid sequence of ATP2A2_586-603

[0377] SEQ ID NO: 307 Amino acid sequence of ATP2A2_604-611

[0378] SEQ ID NO: 308 Amino acid sequence of ATP2A2_637-650

[0379] SEQ ID NO: 309 Amino acid sequence of ATP2A2_638-650

[0380] SEQ ID NO: 310 Amino acid sequence of ATP2A2_656-666

[0381] SEQ ID NO: 311 Amino acid sequence of ATP2A2_667-673 SEQ ID NO: 312 Amino acid sequence of ATP2A2_686-711 SEQ ID NO: 313 Amino acid sequence of ATP2A2_989-1003 SEQ ID NO: 314 Amino acid sequence of CDS2_8-19 SEQ ID NO: 315 Amino acid sequence of CDS2_27-38 SEQ ID NO: 316 Amino acid sequence of CNDP2_10-17 SEQ ID NO: 317 Amino acid sequence of CNDP2_44-53 SEQ ID NO: 318 Amino acid sequence of CNDP2_54-66 SEQ ID NO: 319 Amino acid sequence of CNDP2_67-84 SEQ ID NO: 320 Amino acid sequence of CNDP2_69-84 SEQ ID NO: 321 Amino acid sequence of CNDP2_93-121 SEQ ID NO: 322 Amino acid sequence of CNDP2_129-149 SEQ ID NO: 323 Amino acid sequence of CNDP2_150-159 SEQ ID NO: 324 Amino acid sequence of CNDP2_160-180 SEQ ID NO: 325 Amino acid sequence of CNDP2_254-275 SEQ ID NO: 326 Amino acid sequence of CNDP2_255-275 SEQ ID NO: 327 Amino acid sequence of CNDP2_276-289 SEQ ID NO: 328 Amino acid sequence of CNDP2_290-301 SEQ ID NO: 329 Amino acid sequence of CNDP2_344-363 SEQ ID NO: 330 Amino acid sequence of CNDP2_403-413 SEQ ID NO: 331 Amino acid sequence of CNDP2_414-430 SEQ ID NO: 332 Amino acid sequence of CNDP2_431-450 SEQ ID NO: 333 Amino acid sequence of CNDP2_454-461 SEQ ID NO: 334 Amino acid sequence of CNDP2_462-475 SEQ ID NO: 335 Amino acid sequence of CTSZ_70-81 SEQ ID NO: 336 Amino acid sequence of CTSZ_190-199 SEQ ID NO: 337 Amino acid sequence of CTSZ_261-270 SEQ ID NO: 338 Amino acid sequence of CTSZ-288-303 SEQ ID NO: 339 Amino acid sequence of DECRl_43-49 SEQ ID NO: 340 Amino acid sequence of DECRl_61-73 SEQ ID NO: 341 Amino acid sequence of DECR1_74-91 SEQ ID NO: 342 Amino acid sequence of DECR1_98-11O SEQ ID NO: 343 Amino acid sequence of DECRl_120-133 SEQ ID NO: 344 Amino acid sequence of DECR1_134-155 SEQ ID NO: 345 Amino acid sequence of DECR1_156-162 SEQ ID NO: 346 Amino acid sequence of DECR1_223-23O SEQ ID NO: 347 Amino acid sequence of DECRl_235-244 SEQ ID NO: 348 Ammo acid sequence of DECR1_252-26O

[0382] SEQ ID NO: 349 Amino acid sequence of DECR1_299-316

[0383] SEQ ID NO: 350 Amino acid sequence of DECRl_320-330

[0384] SEQ ID NO: 351 Amino acid sequence of ERP29_37-48

[0385] SEQ ID NO: 352 Amino acid sequence of ERP29_60-69

[0386] SEQ ID NO: 353 Amino acid sequence of ERP29_100-107

[0387] SEQ ID NO: 354 Amino acid sequence of ERP29_113-122

[0388] SEQ ID NO: 355 Amino acid sequence of ERP29_123-137

[0389] SEQ ID NO: 356 Amino acid sequence of ERP29_147-170

[0390] SEQ ID NO: 357 Amino acid sequence of ERP29_183-192

[0391] SEQ ID NO: 358 Amino acid sequence of ERP29_198-204

[0392] SEQ ID NO: 359 Amino acid sequence of ERP29_209-223

[0393] SEQ ID NO: 360 Amino acid sequence of ERP29_244-253

[0394] SEQ ID NO: 361 Amino acid sequence of GAPVD1_1O9-119

[0395] SEQ ID NO: 362 Amino acid sequence of GAPVDl_339-346

[0396] SEQ ID NO: 363 Amino acid sequence of GAPVD1_387-404

[0397] SEQ ID NO: 364 Amino acid sequence of GAPVDl_637-645

[0398] SEQ ID NO: 365 Amino acid sequence of GAPVDl_735-754

[0399] SEQ ID NO: 366 Amino acid sequence of GAPVDl_787-796

[0400] SEQ ID NO: 367 Amino acid sequence of GAPVDl_902-910

[0401] SEQ ID NO: 368 Amino acid sequence of GAPVDl_1011-1021

[0402] SEQ ID NO: 369 Amino acid sequence of GAPVD1_1126-1144

[0403] SEQ ID NO: 370 Amino acid sequence of GAPVD1_1211-1219

[0404] SEQ ID NO: 371 Amino acid sequence of GAPVDl_1361-1370

[0405] SEQ ID NO: 372 Amino acid sequence of GAPVD1_1371-1382

[0406] SEQ ID NO: 373 Amino acid sequence of GARSl_53-68

[0407] SEQ ID NO: 374 Amino acid sequence of GARS1_159-166

[0408] SEQ ID NO: 375 Amino acid sequence of GARS1_167-19O

[0409] SEQ ID NO: 376 Amino acid sequence of GARS1_198-2O4

[0410] SEQ ID NO: 377 Amino acid sequence of GARS 1_311-318

[0411] SEQ ID NO: 378 Amino acid sequence of GARS 1_319-331

[0412] SEQ ID NO: 379 Amino acid sequence of GARSl_345-360

[0413] SEQ ID NO: 380 Amino acid sequence of GARS1_392-412

[0414] SEQ ID NO: 381 Amino acid sequence of GARS1_413-419

[0415] SEQ ID NO: 382 Amino acid sequence of GARS 1_451-464

[0416] SEQ ID NO: 383 Amino acid sequence of GARSl_465-474 SEQ ID NO: 384 Amino acid sequence of GARS 1_491-501

[0417] SEQ ID NO: 385 Amino acid sequence of GARS 1_538-547

[0418] SEQ ID NO: 386 Amino acid sequence of GARSl_564-583

[0419] SEQ ID NO: 387 Amino acid sequence of GARSl_584-596

[0420] SEQ ID NO: 388 Amino acid sequence of GARSl_603-615

[0421] SEQ ID NO: 389 Amino acid sequence of GARS 1_616-632

[0422] SEQ ID NO: 390 Amino acid sequence of GARSl_633-640

[0423] SEQ ID NO: 391 Amino acid sequence of GARSl_647-656

[0424] SEQ ID NO: 392 Amino acid sequence of GARSl_680-687

[0425] SEQ ID NO: 393 Amino acid sequence of GARSl_697-722

[0426] SEQ ID NO: 394 Amino acid sequence of GARSl_723-733

[0427] SEQ ID NO: 395 Amino acid sequence of GARSl_723-734

[0428] SEQ ID NO: 396 Amino acid sequence of HLA-A_31-38

[0429] SEQ ID NO: 397 Amino acid sequence of HLA-A_31-41

[0430] SEQ ID NO: 398 Amino acid sequence of HLA-A_46-59

[0431] SEQ ID NO: 399 Amino acid sequence of HLA-A_60-68

[0432] SEQ ID NO: 400 Amino acid sequence of HLA-A_73-89

[0433] SEQ ID NO: 401 Amino acid sequence of HLA-A_93-106

[0434] SEQ ID NO: 402 Amino acid sequence of HLA-A_139-155

[0435] SEQ ID NO: 403 Amino acid sequence of HLA-A_170-181

[0436] SEQ ID NO: 404 Amino acid sequence of HLA-A_171-181

[0437] SEQ ID NO: 405 Amino acid sequence of HLA-A_182-193

[0438] SEQ ID NO: 406 Amino acid sequence of HLA-A_341-365

[0439] SEQ ID NO: 407 Amino acid sequence of KRT17_7-15

[0440] SEQ ID NO: 408 Amino acid sequence of KRT17_7-26

[0441] SEQ ID NO: 409 Amino acid sequence of KRT17_16-26

[0442] SEQ ID NO: 410 Amino acid sequence of KRT17_31-41

[0443] SEQ ID NO: 411 Amino acid sequence of KRT17_104-l 15

[0444] SEQ ID NO: 412 Amino acid sequence of KRT17_130-136

[0445] SEQ ID NO: 413 Amino acid sequence of KRT17_137-144

[0446] SEQ ID NO: 414 Amino acid sequence of KRT17_137-163

[0447] SEQ ID NO: 415 Amino acid sequence of KRT17_145-163

[0448] SEQ ID NO: 416 Amino acid sequence of KRT17_181-191

[0449] SEQ ID NO: 417 Amino acid sequence of KRT17_181-192

[0450] SEQ ID NO: 418 Amino acid sequence of KRT17_202-212

[0451] SEQ ID NO: 419 Amino acid sequence of KRT17_231-251 SEQ ID NO: 420 Amino acid sequence of KRT17_269-278

[0452] SEQ ID NO: 421 Amino acid sequence of KRT17_270-278

[0453] SEQ ID NO: 422 Amino acid sequence of KRT17_306-321

[0454] SEQ ID NO: 423 Amino acid sequence of KRT17_322-334

[0455] SEQ ID NO: 424 Amino acid sequence of KRT17_335-357

[0456] SEQ ID NO: 425 Amino acid sequence of KRT17_386-399

[0457] SEQ ID NO: 426 Amino acid sequence of KRT17_387-399

[0458] SEQ ID NO: 427 Amino acid sequence of KRT17_387-400

[0459] SEQ ID NO: 428 Amino acid sequence of KRT17_410-419

[0460] SEQ ID NO: 429 Amino acid sequence of KRT17_410-424

[0461] SEQ ID NO: 430 Amino acid sequence of LAP3_35-43

[0462] SEQ ID NO: 431 Amino acid sequence of LAP3_44-61

[0463] SEQ ID NO: 432 Amino acid sequence of LAP3_46-61

[0464] SEQ ID NO: 433 Amino acid sequence of LAP3_67-79

[0465] SEQ ID NO: 434 Amino acid sequence of LAP3_69-79

[0466] SEQ ID NO: 435 Amino acid sequence of LAP3_85-103

[0467] SEQ ID NO: 436 Amino acid sequence of LAP3_105-118

[0468] SEQ ID NO: 437 Amino acid sequence of LAP3_105-122

[0469] SEQ ID NO: 438 Amino acid sequence of LAP3_177-188

[0470] SEQ ID NO: 439 Amino acid sequence of LAP3_ 189-200

[0471] SEQ ID NO: 440 Amino acid sequence of LAP3_201-214

[0472] SEQ ID NO: 441 Amino acid sequence of LAP3_215-221

[0473] SEQ ID NO: 442 Amino acid sequence of LAP3_230-237

[0474] SEQ ID NO: 443 Amino acid sequence of LAP3_238-253

[0475] SEQ ID NO: 444 Amino acid sequence of LAP3_254-267

[0476] SEQ ID NO: 445 Amino acid sequence of LAP3_268-282

[0477] SEQ ID NO: 446 Amino acid sequence of LAP3_283-294

[0478] SEQ ID NO: 447 Amino acid sequence of LAP3_295-303

[0479] SEQ ID NO: 448 Amino acid sequence of LAP3_304-321

[0480] SEQ ID NO: 449 Amino acid sequence of LAP3_322-342

[0481] SEQ ID NO: 450 Amino acid sequence of LAP3_357-368

[0482] SEQ ID NO: 451 Amino acid sequence of LAP3_369-384

[0483] SEQ ID NO: 452 Amino acid sequence of LAP3_418-428

[0484] SEQ ID NO: 453 Amino acid sequence of LAP3_432-440

[0485] SEQ ID NO: 454 Amino acid sequence of LAP3_441-455

[0486] SEQ ID NO: 455 Amino acid sequence of LAP3_458-469 SEQ ID NO: 456 Amino acid sequence of LAP3_477-489

[0487] SEQ ID NO: 457 Amino acid sequence of LAP3_506-513

[0488] SEQ ID NO: 458 Amino acid sequence of LMNBl_15-26

[0489] SEQ ID NO: 459 Amino acid sequence of LMNBl_43-49

[0490] SEQ ID NO: 460 Amino acid sequence of LMNBl_52-67

[0491] SEQ ID NO: 461 Amino acid sequence of LMNB1_74-9O

[0492] SEQ ID NO: 462 Amino acid sequence of LMNB1_8O-9O

[0493] SEQ ID NO: 463 Amino acid sequence of LMNB1_8O-91

[0494] SEQ ID NO: 464 Amino acid sequence of LMNBl_91-98

[0495] SEQ ID NO: 465 Amino acid sequence of LMNB1_1O3-1O9

[0496] SEQ ID NO: 466 Amino acid sequence of LMNB1_112-123

[0497] SEQ ID NO: 467 Amino acid sequence of LMNB1_125-134

[0498] SEQ ID NO: 468 Amino acid sequence of LMNB 1_135-145

[0499] SEQ ID NO: 469 Amino acid sequence of LMNB1_137-145

[0500] SEQ ID NO: 470 Amino acid sequence of LMNB1_146-156

[0501] SEQ ID NO: 471 Amino acid sequence of LMNB1_146-157

[0502] SEQ ID NO: 472 Amino acid sequence of LMNB1_183-191

[0503] SEQ ID NO: 473 Amino acid sequence of LMNBl_198-208

[0504] SEQ ID NO: 474 Amino acid sequence of LMNB1_198-2O9

[0505] SEQ ID NO: 475 Amino acid sequence of LMNBl_209-220

[0506] SEQ ID NO: 476 Amino acid sequence of LMNBl_210-220

[0507] SEQ ID NO: 477 Amino acid sequence of LMNB1_21O-221

[0508] SEQ ID NO: 478 Amino acid sequence of LMNBl_227-234

[0509] SEQ ID NO: 479 Amino acid sequence of LMNB1_235-241

[0510] SEQ ID NO: 480 Amino acid sequence of LMNB1_242-25O

[0511] SEQ ID NO: 481 Amino acid sequence of LMNB1_259-271

[0512] SEQ ID NO: 482 Amino acid sequence of LMNB 1_262-271

[0513] SEQ ID NO: 483 Amino acid sequence of LMNB1_277-29O

[0514] SEQ ID NO: 484 Amino acid sequence of LMNB1_291-297

[0515] SEQ ID NO: 485 Amino acid sequence of LMNB1_298-312

[0516] SEQ ID NO: 486 Amino acid sequence of LMNB1_3OO-312

[0517] SEQ ID NO: 487 Amino acid sequence of LMNBl_321-330

[0518] SEQ ID NO: 488 Amino acid sequence of LMNB1_351-367

[0519] SEQ ID NO: 489 Amino acid sequence of LMNBl_368-378

[0520] SEQ ID NO: 490 Amino acid sequence of LMNBl_368-379

[0521] SEQ ID NO: 491 Amino acid sequence of LMNBl_456-473 SEQ ID NO: 492 Amino acid sequence of LMNBl_458-473

[0522] SEQ ID NO: 493 Amino acid sequence of LMNBl_474-483

[0523] SEQ ID NO: 494 Amino acid sequence of LMNBl_475-483

[0524] SEQ ID NO: 495 Amino acid sequence of LMNB1_492-516

[0525] SEQ ID NO: 496 Amino acid sequence of LMNB 1_517-528

[0526] SEQ ID NO: 497 Amino acid sequence of LMNBl_533-542

[0527] SEQ ID NO: 498 Amino acid sequence of LMNBl_548-577

[0528] SEQ ID NO: 499 Amino acid sequence of MMP2_128-146

[0529] SEQ ID NO: 500 Amino acid sequence of MMP2_147-158

[0530] SEQ ID NO: 501 Amino acid sequence of MMP2_162-175

[0531] SEQ ID NO: 502 Amino acid sequence of MVP_ 10-27

[0532] SEQ ID NO: 503 Amino acid sequence of MVP_43-49

[0533] SEQ ID NO: 504 Amino acid sequence of MVP_50-56

[0534] SEQ ID NO: 505 Amino acid sequence of MVP_57-67

[0535] SEQ ID NO: 506 Amino acid sequence of MVP_68-82

[0536] SEQ ID NO: 507 Amino acid sequence of MVP_85-91

[0537] SEQ ID NO: 508 Amino acid sequence of MVP_92-107

[0538] SEQ ID NO: 509 Amino acid sequence of MVP_108-124

[0539] SEQ ID NO: 510 Amino acid sequence of MVP_125-132

[0540] SEQ ID NO: 511 Amino acid sequence of MVP_137-154

[0541] SEQ ID NO: 512 Amino acid sequence of MVP_155-169

[0542] SEQ ID NO: 513 Amino acid sequence of MVP_156-169

[0543] SEQ ID NO: 514 Amino acid sequence of MVP_307-335

[0544] SEQ ID NO: 515 Amino acid sequence of MVP_336-348

[0545] SEQ ID NO: 516 Amino acid sequence of MVP_349-360

[0546] SEQ ID NO: 517 Amino acid sequence of MVP_361-370

[0547] SEQ ID NO: 518 Amino acid sequence of MVP_371-377

[0548] SEQ ID NO: 519 Amino acid sequence of MVP_378-394

[0549] SEQ ID NO: 520 Amino acid sequence of MVP_400-417

[0550] SEQ ID NO: 521 Amino acid sequence of MVP_418-429

[0551] SEQ ID NO: 522 Amino acid sequence of MVP_430-437

[0552] SEQ ID NO: 523 Amino acid sequence of MVP_445-452

[0553] SEQ ID NO: 524 Amino acid sequence of MVP_462-474

[0554] SEQ ID NO: 525 Amino acid sequence of MVP_480-504

[0555] SEQ ID NO: 526 Amino acid sequence of MVP_480-506

[0556] SEQ ID NO: 527 Amino acid sequence of MVP_512-536 SEQ ID NO: 528 Amino acid sequence of MVP_513-536

[0557] SEQ ID NO: 529 Amino acid sequence of MVP_561-573

[0558] SEQ ID NO: 530 Amino acid sequence of MVP_579-593

[0559] SEQ ID NO: 531 Amino acid sequence of MVP_581-593

[0560] SEQ ID NO: 532 Amino acid sequence of MVP_601-612

[0561] SEQ ID NO: 533 Amino acid sequence of MVP_613-621

[0562] SEQ ID NO: 534 Amino acid sequence of MVP_624-649

[0563] SEQ ID NO: 535 Amino acid sequence of MVP_657-674

[0564] SEQ ID NO: 536 Amino acid sequence of MVP_693-701

[0565] SEQ ID NO: 537 Amino acid sequence of MVP_704-723

[0566] SEQ ID NO: 538 Amino acid sequence of MVP_705-723

[0567] SEQ ID NO: 539 Amino acid sequence of MVP_735-745

[0568] SEQ ID NO: 540 Amino acid sequence of MVP_748-761

[0569] SEQ ID NO: 541 Amino acid sequence of MVP_765-774

[0570] SEQ ID NO: 542 Amino acid sequence of MVP_767-774

[0571] SEQ ID NO: 543 Amino acid sequence of MVP_775-783

[0572] SEQ ID NO: 544 Amino acid sequence of MVP_784-793

[0573] SEQ ID NO: 545 Amino acid sequence of MVP_797-808

[0574] SEQ ID NO: 546 Amino acid sequence of MVP_809-820

[0575] SEQ ID NO: 547 Amino acid sequence of MVP_821-828

[0576] SEQ ID NO: 548 Amino acid sequence of NOP56_91-99

[0577] SEQ ID NO: 549 Amino acid sequence of NOP56_135-143

[0578] SEQ ID NO: 550 Amino acid sequence of NOP56_203-212

[0579] SEQ ID NO: 551 Amino acid sequence of NOP56_213-220

[0580] SEQ ID NO: 552 Amino acid sequence of NOP56_271-278

[0581] SEQ ID NO: 553 Amino acid sequence of NOP56_279-286

[0582] SEQ ID NO: 554 Amino acid sequence of NOP56_289-307

[0583] SEQ ID NO: 555 Amino acid sequence of NOP56_308-320

[0584] SEQ ID NO: 556 Amino acid sequence of NOP56_321-333

[0585] SEQ ID NO: 557 Amino acid sequence of NOP56_348-359

[0586] SEQ ID NO: 558 Amino acid sequence of NOP56_382-396

[0587] SEQ ID NO: 559 Amino acid sequence of NOP56_405-415

[0588] SEQ ID NO: 560 Amino acid sequence of NOP56_405-416

[0589] SEQ ID NO: 561 Amino acid sequence of NOP56_423-437

[0590] SEQ ID NO: 562 Amino acid sequence of NOP56_541-553

[0591] SEQ ID NO: 563 Amino acid sequence of NOP56_565-578 SEQ ID NO: 564 Amino acid sequence of OPA3_154-160

[0592] SEQ ID NO: 565 Amino acid sequence of OPA3_161-168

[0593] SEQ ID NO: 566 Amino acid sequence of PSMB4_46-60

[0594] SEQ ID NO: 567 Amino acid sequence of PSMB4_61-80

[0595] SEQ ID NO: 568 Amino acid sequence of PSMB4_90-109

[0596] SEQ ID NO: 569 Amino acid sequence of PSMB4_110-131

[0597] SEQ ID NO: 570 Amino acid sequence of PSMB4_132-139

[0598] SEQ ID NO: 571 Amino acid sequence of PSMB4_197-211

[0599] SEQ ID NO: 572 Amino acid sequence of PSMB4_202-211

[0600] SEQ ID NO: 573 Amino acid sequence of PSMB4_232-240

[0601] SEQ ID NO: 574 Amino acid sequence of PSMB4_241-264

[0602] SEQ ID NO: 575 Amino acid sequence of S 100A4_8-18

[0603] SEQ ID NO: 576 Amino acid sequence of S 100A4_41-48

[0604] SEQ ID NO: 577 Amino acid sequence of S 100A4_49-57

[0605] SEQ ID NO: 578 Amino acid sequence of S 100A4_50-57

[0606] SEQ ID NO: 579 Amino acid sequence of S 100A4_58-66

[0607] SEQ ID NO: 580 Amino acid sequence of SPRR3_8-22

[0608] SEQ ID NO: 581 Amino acid sequence of SPRR3_23-38

[0609] SEQ ID NO: 582 Amino acid sequence of SPRR3_45-52

[0610] SEQ ID NO: 583 Amino acid sequence of SPRR3_45-60

[0611] SEQ ID NO: 584 Amino acid sequence of SPRR3_53-60

[0612] SEQ ID NO: 585 Amino acid sequence of SPRR3_53-68

[0613] SEQ ID NO: 586 Amino acid sequence of SPRR3_61-68

[0614] SEQ ID NO: 587 Amino acid sequence of SPRR3_61-76

[0615] SEQ ID NO: 588 Amino acid sequence of SPRR3_93-108

[0616] SEQ ID NO: 589 Amino acid sequence of SPRR3_101-108

[0617] SEQ ID NO: 590 Amino acid sequence of SPRR3_ 101-116

[0618] SEQ ID NO: 591 Amino acid sequence of SPRR3_ 109-116

[0619] SEQ ID NO: 592 Amino acid sequence of SPRR3_109-124

[0620] SEQ ID NO: 593 Amino acid sequence of SPRR3_ 117-124

[0621] SEQ ID NO: 594 Amino acid sequence of SPRR3_ 117-132

[0622] SEQ ID NO: 595 Amino acid sequence of SPRR3_125-132

[0623] SEQ ID NO: 596 Amino acid sequence of SPRR3_125-140

[0624] SEQ ID NO: 597 Amino acid sequence of SPRR3_133-140

[0625] SEQ ID NO: 598 Amino acid sequence of SPRR3_141-148

[0626] SEQ ID NO: 599 Amino acid sequence of SPRR3_141-165 SEQ ID NO: 600 Amino acid sequence of SPRR3_149-165

[0627] SEQ ID NO: 601 Amino acid sequence of TCEAl_20-29

[0628] SEQ ID NO: 602 Amino acid sequence of TCEAl_33-45

[0629] SEQ ID NO: 603 Amino acid sequence of TCEAl_46-54

[0630] SEQ ID NO: 604 Amino acid sequence of TCEAl_56-67

[0631] SEQ ID NO: 605 Amino acid sequence of TCEAl_105-116

[0632] SEQ ID NO: 606 Amino acid sequence of TCEA1_124-132

[0633] SEQ ID NO: 607 Amino acid sequence of TCEA1_133-141

[0634] SEQ ID NO: 608 Amino acid sequence of TCEA1_146-153

[0635] SEQ ID NO: 609 Amino acid sequence of TCEA1_154-181

[0636] SEQ ID NO: 610 Amino acid sequence of TCEAl_223-234

[0637] SEQ ID NO: 611 Amino acid sequence of TCEAl_280-297

[0638] SEQ ID NO: 612 Amino acid sequence of WDR81_44-61

[0639] SEQ ID NO: 613 Amino acid sequence of WDR81_79-88

[0640] SEQ ID NO: 614 Amino acid sequence of WDR81_98-104

[0641] SEQ ID NO: 615 Amino acid sequence of WDR81_138-148

[0642] SEQ ID NO: 616 Amino acid sequence of WDR81_211-220

[0643] SEQ ID NO: 617 Amino acid sequence of WDR81_322-346

[0644] SEQ ID NO: 618 Amino acid sequence of WDR81_592-607

[0645] SEQ ID NO: 619 Amino acid sequence of WDR81_706-718

[0646] SEQ ID NO: 620 Amino acid sequence of WDR81_744-756

[0647] SEQ ID NO: 621 Amino acid sequence of WDR81_757-769

[0648] SEQ ID NO: 622 Amino acid sequence of WDR81_789-799

[0649] SEQ ID NO: 623 Amino acid sequence of WDR81_1252-1262

[0650] SEQ ID NO: 624 Amino acid sequence of WDR81_ 1780- 1790

[0651] SEQ ID NO: 625 Amino acid sequence of WDR81_1791-1799

[0652] SEQ ID NO: 626 Amino acid sequence of WDR81_ 1927- 1938

[0653] SEQ ID NO: 627 Amino acid sequence of ACTB

[0654] SEQ ID NO: 628 Amino acid sequence of ATP5F1B

[0655] SEQ ID NO: 629 Amino acid sequence of ATP5F1D

[0656] SEQ ID NO: 630 Amino acid sequence of CDKN2A

[0657] SEQ ID NO: 631 Amino acid sequence of DARS2

[0658] SEQ ID NO: 632 Amino acid sequence of EMILIN 1

[0659] SEQ ID NO: 633 Amino acid sequence of ENO 1

[0660] SEQ ID NO: 634 Amino acid sequence of EPPKl

[0661] SEQ ID NO: 635 Amino acid sequence of FN1 SEQ ID NO: 636 Amino acid sequence of GNAI3

[0662] SEQ ID NO: 637 Amino acid sequence of GNL1

[0663] SEQ ID NO: 638 Amino acid sequence of GSR

[0664] SEQ ID NO: 639 Amino acid sequence of IGKVl-6

[0665] SEQ ID NO: 640 Amino acid sequence of KRT6C

[0666] SEQ ID NO: 641 Amino acid sequence of MUC5B

[0667] SEQ ID NO: 642 Amino acid sequence of MYH11

[0668] SEQ ID NO: 643 Amino acid sequence of OXCT1

[0669] SEQ ID NO: 644 Amino acid sequence of PKP2

[0670] SEQ ID NO: 645 Amino acid sequence of POSTN

[0671] SEQ ID NO: 646 Amino acid sequence of PRKDC

[0672] SEQ ID NO: 647 Amino acid sequence of PTBPl

[0673] SEQ ID NO: 648 Amino acid sequence of PTBP3

[0674] SEQ ID NO: 649 Amino acid sequence of RPS4X

[0675] SEQ ID NO: 650 Amino acid sequence of SIK3

[0676] SEQ ID NO: 651 Amino acid sequence of STAG 1

[0677] SEQ ID NO: 652 Amino acid sequence of TNC

[0678] SEQ ID NO: 653 Amino acid sequence of ACTB_257-290

[0679] SEQ ID NO: 654 Amino acid sequence of ATP5F1B_63-91

[0680] SEQ ID NO: 655 Amino acid sequence of ATP5F1B_95-1O9

[0681] SEQ ID NO: 656 Amino acid sequence of ATP5F1B_110-121

[0682] SEQ ID NO: 657 Amino acid sequence of ATP5F1B_125-133

[0683] SEQ ID NO: 658 Amino acid sequence of ATP5F1B_125-143

[0684] SEQ ID NO: 659 Amino acid sequence of ATP5F1B_134-143

[0685] SEQ ID NO: 660 Amino acid sequence of ATP5F1B_144-155

[0686] SEQ ID NO: 661 Amino acid sequence of ATP5F1B_162-188

[0687] SEQ ID NO: 662 Amino acid sequence of ATP5F1B_189-198

[0688] SEQ ID NO: 663 Amino acid sequence of ATP5F1B_2O2-212

[0689] SEQ ID NO: 664 Amino acid sequence of ATP5F1B_213-225

[0690] SEQ ID NO: 665 Amino acid sequence of ATP5FlB_226-239

[0691] SEQ ID NO: 666 Amino acid sequence of ATP5FlB_242-259

[0692] SEQ ID NO: 667 Amino acid sequence of ATP5FlB_260-279

[0693] SEQ ID NO: 668 Amino acid sequence of ATP5FlB_265-279

[0694] SEQ ID NO: 669 Amino acid sequence of ATP5FlB_282-294

[0695] SEQ ID NO: 670 Amino acid sequence of ATP5FlB_295-310

[0696] SEQ ID NO: 671 Amino acid sequence of ATP5F1B_311-324 SEQ ID NO: 672 Amino acid sequence of ATP5FlB_325-345

[0697] SEQ ID NO: 673 Amino acid sequence of ATP5FlB_388-406

[0698] SEQ ID NO: 674 Amino acid sequence of ATP5FlB_407-422

[0699] SEQ ID NO: 675 Amino acid sequence of ATP5F1B_433-451

[0700] SEQ ID NO: 676 Amino acid sequence of ATP5FlB_433-456

[0701] SEQ ID NO: 677 Amino acid sequence of ATP5FlB_463-480

[0702] SEQ ID NO: 678 Amino acid sequence of ATP5F1B_481-489

[0703] SEQ ID NO: 679 Amino acid sequence of ATP5F1B_49O-519

[0704] SEQ ID NO: 680 Amino acid sequence of ATP5F1B_325-351

[0705] SEQ ID NO: 681 Amino acid sequence of ATP5F1D_57-81

[0706] SEQ ID NO: 682 Amino acid sequence of ATP5FlD_137-150

[0707] SEQ ID NO: 683 Amino acid sequence of ATP5F1D_157-165

[0708] SEQ ID NO: 684 Amino acid sequence of ATP5FlD_15-56

[0709] SEQ ID NO: 685 Amino acid sequence of CDKN2A_30-46

[0710] SEQ ID NO: 686 Amino acid sequence of CDKN2A_47-58

[0711] SEQ ID NO: 687 Amino acid sequence of CDKN2A_113-124

[0712] SEQ ID NO: 688 Amino acid sequence of CDKN2A_145-156

[0713] SEQ ID NO: 689 Amino acid sequence of CDKN2A_2-22

[0714] SEQ ID NO: 690 Amino acid sequence of DARS2_40-50

[0715] SEQ ID NO: 691 Amino acid sequence of DARS2_41-50

[0716] SEQ ID NO: 692 Amino acid sequence of DARS2_51-58

[0717] SEQ ID NO: 693 Amino acid sequence of DARS2_77-84

[0718] SEQ ID NO: 694 Amino acid sequence of DARS2_106-125

[0719] SEQ ID NO: 695 Amino acid sequence of DARS2_180-188

[0720] SEQ ID NO: 696 Amino acid sequence of DARS2_248-257

[0721] SEQ ID NO: 697 Amino acid sequence of DARS2_341-349

[0722] SEQ ID NO: 698 Amino acid sequence of DARS2_369-377

[0723] SEQ ID NO: 699 Amino acid sequence of DARS2.389-408

[0724] SEQ ID NO: 700 Amino acid sequence of DARS2_409-423

[0725] SEQ ID NO: 701 Amino acid sequence of DARS2_429-447

[0726] SEQ ID NO: 702 Amino acid sequence of DARS2_455-466

[0727] SEQ ID NO: 703 Amino acid sequence of DARS2_457-466

[0728] SEQ ID NO: 704 Amino acid sequence of DARS2_588-599

[0729] SEQ ID NO: 705 Amino acid sequence of EMILIN 1_28-51

[0730] SEQ ID NO: 706 Amino acid sequence of EMILIN1_178-19O

[0731] SEQ ID NO: 707 Amino acid sequence of EMILIN 1 197-205 SEQ ID NO: 708 Amino acid sequence of EMILIN l_206-212

[0732] SEQ ID NO: 709 Amino acid sequence of EMILIN1_213-221

[0733] SEQ ID NO: 710 Amino acid sequence of EMILIN l_222-230

[0734] SEQ ID NO: 711 Amino acid sequence of EMILIN l_276-292

[0735] SEQ ID NO: 712 Amino acid sequence of EMILINl_329-336

[0736] SEQ ID NO: 713 Amino acid sequence of EMILINl_339-347

[0737] SEQ ID NO: 714 Amino acid sequence of EMILINl_368-382

[0738] SEQ ID NO: 715 Amino acid sequence of EMILINl_369-382

[0739] SEQ ID NO: 716 Amino acid sequence of EMILINl_383-406

[0740] SEQ ID NO: 717 Amino acid sequence of EMILIN 1_384-406

[0741] SEQ ID NO: 718 Amino acid sequence of EMILINl_503-512

[0742] SEQ ID NO: 719 Amino acid sequence of EMILIN l_504-512

[0743] SEQ ID NO: 720 Amino acid sequence of EMILIN1_513-528

[0744] SEQ ID NO: 721 Amino acid sequence of EMILIN 1_529-541

[0745] SEQ ID NO: 722 Amino acid sequence of EMILIN l_546-559

[0746] SEQ ID NO: 723 Amino acid sequence of EMILINl_567-594

[0747] SEQ ID NO: 724 Amino acid sequence of EMILIN 1_611-623

[0748] SEQ ID NO: 725 Amino acid sequence of EMILIN 1_685-691

[0749] SEQ ID NO: 726 Amino acid sequence of EMILIN l_692-706

[0750] SEQ ID NO: 727 Amino acid sequence of EMILIN l_709-726

[0751] SEQ ID NO: 728 Amino acid sequence of EMILIN l_737-748

[0752] SEQ ID NO: 729 Amino acid sequence of EMILIN l_754-763

[0753] SEQ ID NO: 730 Amino acid sequence of EMILINl_779-788

[0754] SEQ ID NO: 731 Amino acid sequence of EMILIN1_882-891

[0755] SEQ ID NO: 732 Amino acid sequence of EMILIN l_892-914

[0756] SEQ ID NO: 733 Amino acid sequence of EMILIN 1_915-925

[0757] SEQ ID NO: 734 Amino acid sequence of EMILIN1_843-881

[0758] SEQ ID NO: 735 Amino acid sequence of ENOl_16-28

[0759] SEQ ID NO: 736 Amino acid sequence of ENOl_16-32

[0760] SEQ ID NO: 737 Amino acid sequence of ENOl_33-54

[0761] SEQ ID NO: 738 Amino acid sequence of ENOl_65-80

[0762] SEQ ID NO: 739 Amino acid sequence of ENOl_72-80

[0763] SEQ ID NO: 740 Amino acid sequence of ENO1_72-81

[0764] SEQ ID NO: 741 Amino acid sequence of ENOl_81-89

[0765] SEQ ID NO: 742 Amino acid sequence of ENOl_82-89

[0766] SEQ ID NO: 743 Amino acid sequence of ENO 1 82-92 SEQ ID NO: 744 Amino acid sequence of ENOl_93-103

[0767] SEQ ID NO: 745 Amino acid sequence of ENO1_121-132

[0768] SEQ ID NO: 746 Amino acid sequence of ENO1_133-162

[0769] SEQ ID NO: 747 Amino acid sequence of ENO1_163-179

[0770] SEQ ID NO: 748 Amino acid sequence of ENO1_184-193

[0771] SEQ ID NO: 749 Amino acid sequence of ENOl_203-221

[0772] SEQ ID NO: 750 Amino acid sequence of ENOl_203-228

[0773] SEQ ID NO: 751 Amino acid sequence of ENOl_222-228

[0774] SEQ ID NO: 752 Amino acid sequence of ENOl_222-233

[0775] SEQ ID NO: 753 Amino acid sequence of ENOl_229-239

[0776] SEQ ID NO: 754 Amino acid sequence of ENOl_234-253

[0777] SEQ ID NO: 755 Amino acid sequence of ENOl_240-253

[0778] SEQ ID NO: 756 Amino acid sequence of ENOl_254-262

[0779] SEQ ID NO: 757 Amino acid sequence of ENOl_257-269

[0780] SEQ ID NO: 758 Amino acid sequence of ENOl_270-281

[0781] SEQ ID NO: 759 Amino acid sequence of ENOl_286-306

[0782] SEQ ID NO: 760 Amino acid sequence of ENOl_307-326

[0783] SEQ ID NO: 761 Amino acid sequence of ENOl_307-327

[0784] SEQ ID NO: 762 Amino acid sequence of ENOl_336-343

[0785] SEQ ID NO: 763 Amino acid sequence of ENOl_344-358

[0786] SEQ ID NO: 764 Amino acid sequence of ENOl_359-372

[0787] SEQ ID NO: 765 Amino acid sequence of ENOl_404-412

[0788] SEQ ID NO: 766 Amino acid sequence of EN01_407-420

[0789] SEQ ID NO: 767 Amino acid sequence of ENOl_413-420

[0790] SEQ ID NO: 768 Amino acid sequence of ENOl_413-422

[0791] SEQ ID NO: 769 Amino acid sequence of ENOl_427-434

[0792] SEQ ID NO: 770 Amino acid sequence of EN01_106-120

[0793] SEQ ID NO: 771 Amino acid sequence of EPPK1_25-41

[0794] SEQ ID NO: 772 Amino acid sequence of EPPKl_90-97

[0795] SEQ ID NO: 773 Amino acid sequence of EPPKl_98-109

[0796] SEQ ID NO: 774 Amino acid sequence of EPPK1_118-130

[0797] SEQ ID NO: 775 Amino acid sequence of EPPK1_131-139

[0798] SEQ ID NO: 776 Amino acid sequence of EPPK1_188-199

[0799] SEQ ID NO: 777 Amino acid sequence of EPPKl_200-208

[0800] SEQ ID NO: 778 Amino acid sequence of EPPK1_2O9-217

[0801] SEQ ID NO: 779 Amino acid sequence of EPPKl_221-232 SEQ ID NO: 780 Amino acid sequence of EPPKl_237-262

[0802] SEQ ID NO: 781 Amino acid sequence of EPPKl_266-274

[0803] SEQ ID NO: 782 Amino acid sequence of EPPKl_279-298

[0804] SEQ ID NO: 783 Amino acid sequence of EPPKl_280-298

[0805] SEQ ID NO: 784 Amino acid sequence of EPPKl_280-299

[0806] SEQ ID NO: 785 Amino acid sequence of EPPKl_337-344

[0807] SEQ ID NO: 786 Amino acid sequence of EPPK1_394-4O9

[0808] SEQ ID NO: 787 Amino acid sequence of EPPK1_411-420

[0809] SEQ ID NO: 788 Amino acid sequence of EPPK1_413-42O

[0810] SEQ ID NO: 789 Amino acid sequence of EPPK1_421-430

[0811] SEQ ID NO: 790 Amino acid sequence of EPPK1_431-447

[0812] SEQ ID NO: 791 Amino acid sequence of EPPKl_448-473

[0813] SEQ ID NO: 792 Amino acid sequence of EPPKl_474-484

[0814] SEQ ID NO: 793 Amino acid sequence of EPPK1_489-5O2

[0815] SEQ ID NO: 794 Amino acid sequence of EPPKl_505-524

[0816] SEQ ID NO: 795 Amino acid sequence of EPPK1_525-54O

[0817] SEQ ID NO: 796 Amino acid sequence of EPPKl_545-557

[0818] SEQ ID NO: 797 Amino acid sequence of EPPKl_565-574

[0819] SEQ ID NO: 798 Amino acid sequence of EPPKl_575-585

[0820] SEQ ID NO: 799 Amino acid sequence of EPPK1_595-6O4

[0821] SEQ ID NO: 800 Amino acid sequence of EPPKl_605-623

[0822] SEQ ID NO: 801 Amino acid sequence of EPPK1_624-63O

[0823] SEQ ID NO: 802 Amino acid sequence of EPPKl_633-657

[0824] SEQ ID NO: 803 Amino acid sequence of EPPKl_670-680

[0825] SEQ ID NO: 804 Amino acid sequence of EPPKl_687-708

[0826] SEQ ID NO: 805 Amino acid sequence of EPPKl_747-765

[0827] SEQ ID NO: 806 Amino acid sequence of EPPK1_831-846

[0828] SEQ ID NO: 807 Amino acid sequence of EPPKl_858-866

[0829] SEQ ID NO: 808 Amino acid sequence of EPPKl_867-874

[0830] SEQ ID NO: 809 Amino acid sequence of EPPKl_875-884

[0831] SEQ ID NO: 810 Amino acid sequence of EPPKl_924-936

[0832] SEQ ID NO: 811 Amino acid sequence of EPPKl_925-936

[0833] SEQ ID NO: 812 Amino acid sequence of EPPKl_944-951

[0834] SEQ ID NO: 813 Amino acid sequence of EPPKl_990-1000

[0835] SEQ ID NO: 814 Amino acid sequence of EPPKl_991-1000

[0836] SEQ ID NO: 815 Amino acid sequence of EPPKl 1004-1012 SEQ ID NO: 816 Amino acid sequence of EPPKl_1028-1038 SEQ ID NO: 817 Amino acid sequence of EPPKl_1029-1038 SEQ ID NO: 818 Amino acid sequence of EPPKl_1067-1092 SEQ ID NO: 819 Amino acid sequence of EPPKl_1093-1104 SEQ ID NO: 820 Amino acid sequence of EPPK1_1105-1130 SEQ ID NO: 821 Amino acid sequence of EPPK1_1131-1139 SEQ ID NO: 822 Amino acid sequence of EPPK1_1140-1158 SEQ ID NO: 823 Amino acid sequence of EPPK1_1159-1169 SEQ ID NO: 824 Amino acid sequence of EPPK1_1160-1169 SEQ ID NO: 825 Amino acid sequence of EPPK1_124O-1259 SEQ ID NO: 826 Amino acid sequence of EPPK1_126O-1267 SEQ ID NO: 827 Amino acid sequence of EPPK1_1268-1278 SEQ ID NO: 828 Amino acid sequence of EPPK1_1279-1297 SEQ ID NO: 829 Amino acid sequence of EPPK1_1312-1322 SEQ ID NO: 830 Amino acid sequence of EPPK1_1323-1333 SEQ ID NO: 831 Amino acid sequence of EPPK1_1334-1344 SEQ ID NO: 832 Amino acid sequence of EPPK1_1382-1398 SEQ ID NO: 833 Amino acid sequence of EPPK1_1382-14O1 SEQ ID NO: 834 Amino acid sequence of EPPKl_1402-1409 SEQ ID NO: 835 Amino acid sequence of EPPK1_141O-1418 SEQ ID NO: 836 Amino acid sequence of EPPK1_1485-1491 SEQ ID NO: 837 Amino acid sequence of EPPKl_1500-1514 SEQ ID NO: 838 Amino acid sequence of EPPK1_1515-1522 SEQ ID NO: 839 Amino acid sequence of EPPK1_1543-1555 SEQ ID NO: 840 Amino acid sequence of EPPK1_1566-1584 SEQ ID NO: 841 Amino acid sequence of EPPK1_1585-1592 SEQ ID NO: 842 Amino acid sequence of EPPK1_1594-1621 SEQ ID NO: 843 Amino acid sequence of EPPKl_1623-1630 SEQ ID NO: 844 Amino acid sequence of EPPK1_17O7-1716 SEQ ID NO: 845 Amino acid sequence of EPPK1_1717-1726 SEQ ID NO: 846 Amino acid sequence of EPPK1_1763-1774 SEQ ID NO: 847 Amino acid sequence of EPPK1_1812-1826 SEQ ID NO: 848 Amino acid sequence of EPPK1_1827-1846 SEQ ID NO: 849 Amino acid sequence of EPPK1_1852- 1863 SEQ ID NO: 850 Amino acid sequence of EPPK1_19O9-1918 SEQ ID NO: 851 Amino acid sequence of EPPK1_1949-1965 SEQ ID NO: 852 Amino acid sequence of EPPK1_1974-1995

[0837] SEQ ID NO: 853 Amino acid sequence of EPPKl_2025-2032

[0838] SEQ ID NO: 854 Amino acid sequence of EPPKl_2039-2048

[0839] SEQ ID NO: 855 Amino acid sequence of EPPKl_2054-2062

[0840] SEQ ID NO: 856 Amino acid sequence of EPPKl_2072-2087

[0841] SEQ ID NO: 857 Amino acid sequence of EPPKl_2091-2100

[0842] SEQ ID NO: 858 Amino acid sequence of EPPKl_2091-2101

[0843] SEQ ID NO: 859 Amino acid sequence of EPPK1_21O1-2114

[0844] SEQ ID NO: 860 Amino acid sequence of EPPK1_2102-2114

[0845] SEQ ID NO: 861 Amino acid sequence of EPPK1_2180-2204

[0846] SEQ ID NO: 862 Amino acid sequence of EPPKl_2205-2215

[0847] SEQ ID NO: 863 Amino acid sequence of EPPK1_2218-2234

[0848] SEQ ID NO: 864 Amino acid sequence of EPPKl_2219-2234

[0849] SEQ ID NO: 865 Amino acid sequence of EPPK1_2243-2251

[0850] SEQ ID NO: 866 Amino acid sequence of EPPKl_2252-2277

[0851] SEQ ID NO: 867 Amino acid sequence of EPPKl_2256-2277

[0852] SEQ ID NO: 868 Amino acid sequence of EPPK1_2281-2299

[0853] SEQ ID NO: 869 Amino acid sequence of EPPKl_2385-2402

[0854] SEQ ID NO: 870 Amino acid sequence of EPPKl_2403-2420

[0855] SEQ ID NO: 871 Amino acid sequence of EPPKl_2404-2420

[0856] SEQ ID NO: 872 Amino acid sequence of EPPK1_2421-2432

[0857] SEQ ID NO: 873 Amino acid sequence of EPPKl_2440-2461

[0858] SEQ ID NO: 874 Amino acid sequence of EPPKl_2468-2474

[0859] SEQ ID NO: 875 Amino acid sequence of EPPKl_2475-2501

[0860] SEQ ID NO: 876 Amino acid sequence of EPPKl_2477-2501

[0861] SEQ ID NO: 877 Amino acid sequence of EPPKl_2502-2514

[0862] SEQ ID NO: 878 Amino acid sequence of EPPKl_2533-2547

[0863] SEQ ID NO: 879 Amino acid sequence of EPPKl_2548-2569

[0864] SEQ ID NO: 880 Amino acid sequence of EPPK1_2551-2569

[0865] SEQ ID NO: 881 Amino acid sequence of EPPKl_2570-2585

[0866] SEQ ID NO: 882 Amino acid sequence of EPPK1_2571-2585

[0867] SEQ ID NO: 883 Amino acid sequence of EPPK1_2571-2593

[0868] SEQ ID NO: 884 Amino acid sequence of EPPKl_2586-2593

[0869] SEQ ID NO: 885 Amino acid sequence of EPPKl_2597-2610

[0870] SEQ ID NO: 886 Amino acid sequence of EPPKl_2642-2649

[0871] SEQ ID NO: 887 Amino acid sequence of EPPKl_2656-2672 SEQ ID NO: 888 Amino acid sequence of EPPKl_2673-2696

[0872] SEQ ID NO: 889 Amino acid sequence of EPPKl_2674-2696

[0873] SEQ ID NO: 890 Amino acid sequence of EPPKl_2697-2704

[0874] SEQ ID NO: 891 Amino acid sequence of EPPK1_2715-2734

[0875] SEQ ID NO: 892 Amino acid sequence of EPPK1_2716-2734

[0876] SEQ ID NO: 893 Amino acid sequence of EPPKl_2742-2753

[0877] SEQ ID NO: 894 Amino acid sequence of EPPKl_2742-2754

[0878] SEQ ID NO: 895 Amino acid sequence of EPPK1_3150-3165

[0879] SEQ ID NO: 896 Amino acid sequence of EPPKl_3246-3265

[0880] SEQ ID NO: 897 Amino acid sequence of EPPK1_3681-3699

[0881] SEQ ID NO: 898 Amino acid sequence of EPPK1_4510-4519

[0882] SEQ ID NO: 899 Amino acid sequence of EPPK1_4637-4651

[0883] SEQ ID NO: 900 Amino acid sequence of EPPKl_4670-4687

[0884] SEQ ID NO: 901 Amino acid sequence of EPPKl_5053-5071

[0885] SEQ ID NO: 902 Amino acid sequence of FNl_58-67

[0886] SEQ ID NO: 903 Amino acid sequence of FNl_108-116

[0887] SEQ ID NO: 904 Amino acid sequence of FNl_242-248

[0888] SEQ ID NO: 905 Amino acid sequence of FN1_273-29O

[0889] SEQ ID NO: 906 Amino acid sequence of FNl_370-379

[0890] SEQ ID NO: 907 Amino acid sequence of FN1_398-411

[0891] SEQ ID NO: 908 Amino acid sequence of FNl_480-486

[0892] SEQ ID NO: 909 Amino acid sequence of FN1J556-669

[0893] SEQ ID NO: 910 Amino acid sequence of FNl_670-694

[0894] SEQ ID NO: 911 Amino acid sequence of FN1_831-842

[0895] SEQ ID NO: 912 Amino acid sequence of FNl_834-842

[0896] SEQ ID NO: 913 Amino acid sequence of FN1_9O4-911

[0897] SEQ ID NO: 914 Amino acid sequence of FNl_912-922

[0898] SEQ ID NO: 915 Amino acid sequence of FNl_923-938

[0899] SEQ ID NO: 916 Amino acid sequence of FNl_939-953

[0900] SEQ ID NO: 917 Amino acid sequence of FNl_959-976

[0901] SEQ ID NO: 918 Amino acid sequence of FNl_977-984

[0902] SEQ ID NO: 919 Amino acid sequence of FNl_985-996

[0903] SEQ ID NO: 920 Amino acid sequence of FNl_988-996

[0904] SEQ ID NO: 921 Amino acid sequence of FNl_1022-1028

[0905] SEQ ID NO: 922 Amino acid sequence of FNl_1041-1050

[0906] SEQ ID NO: 923 Amino acid sequence of FNl_1041-1054 SEQ ID NO: 924 Amino acid sequence of FN1_ 1055- 1070

[0907] SEQ ID NO: 925 Amino acid sequence of FNl_1055-1077

[0908] SEQ ID NO: 926 Amino acid sequence of FN1_1117- 1129

[0909] SEQ ID NO: 927 Amino acid sequence of FN1_1121-1129

[0910] SEQ ID NO: 928 Amino acid sequence of FN 1_1130- 1157

[0911] SEQ ID NO: 929 Amino acid sequence of FN l_1170-1197

[0912] SEQ ID NO: 930 Amino acid sequence of FN1_1198- 1207

[0913] SEQ ID NO: 931 Amino acid sequence of FN1_1366-1375

[0914] SEQ ID NO: 932 Amino acid sequence of FN1_1376-1392

[0915] SEQ ID NO: 933 Amino acid sequence of FN1_ 1447- 1473

[0916] SEQ ID NO: 934 Amino acid sequence of FN1_1481-1491

[0917] SEQ ID NO: 935 Amino acid sequence of FN1_1483-1493

[0918] SEQ ID NO: 936 Amino acid sequence of FN1_1494-15O1

[0919] SEQ ID NO: 937 Amino acid sequence of FNl_1502-1525

[0920] SEQ ID NO: 938 Amino acid sequence of FN1_1526-1543

[0921] SEQ ID NO: 939 Amino acid sequence of FN1_1544-1567

[0922] SEQ ID NO: 940 Amino acid sequence of FN1_1571-1591

[0923] SEQ ID NO: 941 Amino acid sequence of FN1_1592-1615

[0924] SEQ ID NO: 942 Amino acid sequence of FNl_1616-1630

[0925] SEQ ID NO: 943 Amino acid sequence of FN1_1624-163O

[0926] SEQ ID NO: 944 Amino acid sequence of FN1_1631-1652

[0927] SEQ ID NO: 945 Amino acid sequence of FN1_ 1653 -1664

[0928] SEQ ID NO: 946 Amino acid sequence of FN1_ 1728- 1740

[0929] SEQ ID NO: 947 Amino acid sequence of FN1_1741-1752

[0930] SEQ ID NO: 948 Amino acid sequence of FN1_1821-1844

[0931] SEQ ID NO: 949 Amino acid sequence of FN1_1858-1878

[0932] SEQ ID NO: 950 Amino acid sequence of FN1_1879- 1887

[0933] SEQ ID NO: 951 Amino acid sequence of FN1_1879-1893

[0934] SEQ ID NO: 952 Amino acid sequence of FN1_1888- 1909

[0935] SEQ ID NO: 953 Amino acid sequence of FN1_1894-19O9

[0936] SEQ ID NO: 954 Amino acid sequence of FN1_1894-191O

[0937] SEQ ID NO: 955 Amino acid sequence of FN1_1913-1926

[0938] SEQ ID NO: 956 Amino acid sequence of FN1_1929-195O

[0939] SEQ ID NO: 957 Amino acid sequence of FN1_1951-1957

[0940] SEQ ID NO: 958 Amino acid sequence of FN1_1958-1971

[0941] SEQ ID NO: 959 Amino acid sequence of FN1_1972-1982 SEQ ID NO: 960 Amino acid sequence of FN1_1983-2OO1

[0942] SEQ ID NO: 961 Amino acid sequence of FNl_2002-2018

[0943] SEQ ID NO: 962 Amino acid sequence of FNl_2021-2027

[0944] SEQ ID NO: 963 Amino acid sequence of FNl_2028-2036

[0945] SEQ ID NO: 964 Amino acid sequence of FNl_2042-2068

[0946] SEQ ID NO: 965 Amino acid sequence of FNl_2082-2110

[0947] SEQ ID NO: 966 Amino acid sequence of FN1_2151-2161

[0948] SEQ ID NO: 967 Amino acid sequence of FN1_2166-2182

[0949] SEQ ID NO: 968 Amino acid sequence of FNl_2241-2255

[0950] SEQ ID NO: 969 Amino acid sequence of FNl_2392-2401

[0951] SEQ ID NO: 970 Amino acid sequence of FNl_2426-2447

[0952] SEQ ID NO: 971 Amino acid sequence of FN1_1366-1392

[0953] SEQ ID NO: 972 Amino acid sequence of GNAI3_71-86

[0954] SEQ ID NO: 973 Amino acid sequence of GNAI3_93-100

[0955] SEQ ID NO: 974 Amino acid sequence of GNAI3_106-128

[0956] SEQ ID NO: 975 Amino acid sequence of GNAI3_133-142

[0957] SEQ ID NO: 976 Amino acid sequence of GNAI3_143-161

[0958] SEQ ID NO: 977 Amino acid sequence of GNAI3_145-161

[0959] SEQ ID NO: 978 Amino acid sequence of GNAI3_162-176

[0960] SEQ ID NO: 979 Amino acid sequence of GNLl_63-74

[0961] SEQ ID NO: 980 Amino acid sequence of GNLl_102-118

[0962] SEQ ID NO: 981 Amino acid sequence of GNL1_119-131

[0963] SEQ ID NO: 982 Amino acid sequence of GNL1_151-158

[0964] SEQ ID NO: 983 Amino acid sequence of GNLl_284-292

[0965] SEQ ID NO: 984 Amino acid sequence of GNLl_293-301

[0966] SEQ ID NO: 985 Amino acid sequence of GNLl_302-308

[0967] SEQ ID NO: 986 Amino acid sequence of GNLl_374-383

[0968] SEQ ID NO: 987 Amino acid sequence of GNLl_409-423

[0969] SEQ ID NO: 988 Amino acid sequence of GNLl_528-545

[0970] SEQ ID NO: 989 Amino acid sequence of GSR_82-89

[0971] SEQ ID NO: 990 Amino acid sequence of GSR_98-110

[0972] SEQ ID NO: 991 Amino acid sequence of GSR_154-164

[0973] SEQ ID NO: 992 Amino acid sequence of GSR_165-171

[0974] SEQ ID NO: 993 Amino acid sequence of GSR_172- 189

[0975] SEQ ID NO: 994 Amino acid sequence of GSR_234-256

[0976] SEQ ID NO: 995 Amino acid sequence of GSR_269-291 SEQ ID NO 996 Amino acid sequence of GSR_300-316

[0977] SEQ ID NO 997 Amino acid sequence of GSR_301-316

[0978] SEQ ID NO 998 Amino acid sequence of GSR_317-335

[0979] SEQ ID NO 999 Amino acid sequence of GSR_347-354

[0980] SEQ ID NO 1000 Amino acid sequence of GSR_355-368

[0981] SEQ ID NO 1001 Amino acid sequence of GSR_369-379

[0982] SEQ ID NO 1002 Amino acid sequence of GSR_380-391

[0983] SEQ ID NO 1003 Amino acid sequence of GSR_380-392

[0984] SEQ ID NO 1004 Amino acid sequence of GSR_435-441

[0985] SEQ ID NO 1005 Amino acid sequence of GSR_442-456

[0986] SEQ ID NO 1006 Amino acid sequence of GSR_474-496

[0987] SEQ ID NO 1007 Amino acid sequence of GSR_502-522

[0988] SEQ ID NO 1008 Amino acid sequence of IGKVl-6_68-83

[0989] SEQ ID NO 1009 Amino acid sequence of KRT6C_401-415

[0990] SEQ ID NO 1010 Amino acid sequence of KRT6C_300-326

[0991] SEQ ID NO 1011 Amino acid sequence of MUC5B_53-75

[0992] SEQ ID NO 1012 Amino acid sequence of MUC5B_76-86

[0993] SEQ ID NO 1013 Amino acid sequence of MUC5B_109-l 19

[0994] SEQ ID NO 1014 Amino acid sequence of MUC5B_109-120

[0995] SEQ ID NO 1015 Amino acid sequence of MUC5B_155-161

[0996] SEQ ID NO 1016 Amino acid sequence of MUC5B_162-174

[0997] SEQ ID NO 1017 Amino acid sequence of MUC5B_226-236

[0998] SEQ ID NO 1018 Amino acid sequence of MUC5B_321-327

[0999] SEQ ID NO 1019 Amino acid sequence of MUC5B_480-493

[1000] SEQ ID NO 1020 Amino acid sequence of MUC5B_602-619

[1001] SEQ ID NO 1021 Amino acid sequence of MUC5B_625-634

[1002] SEQ ID NO 1022 Amino acid sequence of MUC5B_677-684

[1003] SEQ ID NO 1023 Amino acid sequence of MUC5B_781-790

[1004] SEQ ID NO 1024 Amino acid sequence of MUC5B_957-972

[1005] SEQ ID NO 1025 Amino acid sequence of MUC5B_977-985

[1006] SEQ ID NO 1026 Amino acid sequence of MUC5B_1007-1013

[1007] SEQ ID NO 1027 Amino acid sequence of MUC5B_1043-1056

[1008] SEQ ID NO 1028 Amino acid sequence of MUC5B_1224-1233

[1009] SEQ ID NO 1029 Amino acid sequence of MUC5B_1382-1401

[1010] SEQ ID NO 1030 Amino acid sequence of MUC5B_1466-1475

[1011] SEQ ID NO 1031 Amino acid sequence of MUC5B_1520-1532 SEQ ID NO 1032 Amino acid sequence of MUC5B_1578-1586

[1012] SEQ ID NO 1033 Amino acid sequence of MUC5B_1642-1661

[1013] SEQ ID NO 1034 Amino acid sequence of MUC5B_1739-1764

[1014] SEQ ID NO 1035 Amino acid sequence of MUC5B_1866-1875

[1015] SEQ ID NO 1036 Amino acid sequence of MUC5B_1938-1952

[1016] SEQ ID NO 1037 Amino acid sequence of MUC5B_1953-1969

[1017] SEQ ID NO 1038 Amino acid sequence of MUC5B_1970-1994

[1018] SEQ ID NO 1039 Amino acid sequence of MUC5B_2032-2050

[1019] SEQ ID NO 1040 Amino acid sequence of MUC5B_2261-2281

[1020] SEQ ID NO 1041 Amino acid sequence of MUC5B_2346-2361

[1021] SEQ ID NO 1042 Amino acid sequence of MUC5B_2362-2371

[1022] SEQ ID NO 1043 Amino acid sequence of MUC5B_2398-2405

[1023] SEQ ID NO 1044 Amino acid sequence of MUC5B_2510-2526

[1024] SEQ ID NO 1045 Amino acid sequence of MUC5B_2527-2551

[1025] SEQ ID NO 1046 Amino acid sequence of MUC5B_2608-2628

[1026] SEQ ID NO 1047 Amino acid sequence of MUC5B_2629-2643

[1027] SEQ ID NO 1048 Amino acid sequence of MUC5B_2758-2768

[1028] SEQ ID NO 1049 Amino acid sequence of MUC5B_2818-2834

[1029] SEQ ID NO 1050 Amino acid sequence of MUC5B_3024-3038

[1030] SEQ ID NO 1051 Amino acid sequence of MUC5B_3047-3060

[1031] SEQ ID NO 1052 Amino acid sequence of MUC5B_3195-3209

[1032] SEQ ID NO 1053 Amino acid sequence of MUC5B_3227-3251

[1033] SEQ ID NO 1054 Amino acid sequence of MUC5B_4281-4295

[1034] SEQ ID NO 1055 Amino acid sequence of MUC5B_4879-4904

[1035] SEQ ID NO 1056 Amino acid sequence of MUC5B_5135-5141

[1036] SEQ ID NO 1057 Amino acid sequence of MUC5B_5142-5155

[1037] SEQ ID NO 1058 Amino acid sequence of MUC5B_5156-5173

[1038] SEQ ID NO 1059 Amino acid sequence of MUC5B_5174-5187

[1039] SEQ ID NO 1060 Amino acid sequence of MUC5B_5188-5207

[1040] SEQ ID NO 1061 Amino acid sequence of MUC5B_5249-5256

[1041] SEQ ID NO 1062 Amino acid sequence of MUC5B_5753-5762

[1042] SEQ ID NO 1063 Amino acid sequence of MYHl l_19-33

[1043] SEQ ID NO 1064 Amino acid sequence of MYHl l_35-42

[1044] SEQ ID NO 1065 Amino acid sequence of MYHl l_55-67

[1045] SEQ ID NO 1066 Amino acid sequence of MYHl l_87-106

[1046] SEQ ID NO 1067 Amino acid sequence of MYH11_2O7-216 SEQ ID NO 1068 Amino acid sequence of MYHl l_349-362

[1047] SEQ ID NO 1069 Amino acid sequence of MYHl l_381-394

[1048] SEQ ID NO 1070 Amino acid sequence of MYHl l_573-583

[1049] SEQ ID NO 1071 Amino acid sequence of MYHl l_584-594

[1050] SEQ ID NO 1072 Amino acid sequence of MYHl l_625-633

[1051] SEQ ID NO 1073 Amino acid sequence of MYHl l_634-644

[1052] SEQ ID NO 1074 Amino acid sequence of MYHl l_670-677

[1053] SEQ ID NO 1075 Amino acid sequence of MYHl l_687-700

[1054] SEQ ID NO 1076 Amino acid sequence of MYHl l_690-700

[1055] SEQ ID NO 1077 Amino acid sequence of MYHl l_728-738

[1056] SEQ ID NO 1078 Amino acid sequence of MYHl l_745-752

[1057] SEQ ID NO 1079 Amino acid sequence of MYHl l_772-782

[1058] SEQ ID NO 1080 Amino acid sequence of MYHl l_786-798

[1059] SEQ ID NO 1081 Amino acid sequence of MYHl l_890-910

[1060] SEQ ID NO 1082 Amino acid sequence of MYHl l_918-930

[1061] SEQ ID NO 1083 Amino acid sequence of MYH11_931-945

[1062] SEQ ID NO 1084 Amino acid sequence of MYHl l_938-945

[1063] SEQ ID NO 1085 Amino acid sequence of MYHl l_948-966

[1064] SEQ ID NO 1086 Amino acid sequence of MYHl l_1008-1021

[1065] SEQ ID NO 1087 Amino acid sequence of MYHl l_1032-1042

[1066] SEQ ID NO 1088 Amino acid sequence of MYHl l_1099-1106

[1067] SEQ ID NO 1089 Amino acid sequence of MYH 11_ 1115-1131

[1068] SEQ ID NO 1090 Amino acid sequence of MYH11_1153- 1169

[1069] SEQ ID NO 1091 Amino acid sequence of MYH11_1172-118O

[1070] SEQ ID NO 1092 Amino acid sequence of MYHl l_1173-1180

[1071] SEQ ID NO 1093 Amino acid sequence of MYH11_1173-1181

[1072] SEQ ID NO 1094 Amino acid sequence of MYH11_1182-1188

[1073] SEQ ID NO 1095 Amino acid sequence of MYH 11_ 1189- 1198

[1074] SEQ ID NO 1096 Amino acid sequence of MYH11_12O1-1216

[1075] SEQ ID NO 1097 Amino acid sequence of MYH11_1232-1241

[1076] SEQ ID NO 1098 Amino acid sequence of MYH11_1257-1267

[1077] SEQ ID NO 1099 Amino acid sequence of MYH11_1285-13O2

[1078] SEQ ID NO 1100 Amino acid sequence of MYHl l_1309-1329

[1079] SEQ ID NO 1101 Amino acid sequence of MYH 11_ 1346- 1359

[1080] SEQ ID NO 1102 Amino acid sequence of MYH11_1365-1377

[1081] SEQ ID NO 1103 Amino acid sequence of MYHl l_1400-1411 SEQ ID NO 1104 Amino acid sequence of MYH11_ 1425- 1440

[1082] SEQ ID NO 1105 Amino acid sequence of MYH11_1441-1448

[1083] SEQ ID NO 1106 Amino acid sequence of MYH11_1511-1520

[1084] SEQ ID NO 1107 Amino acid sequence of MYH11_1536-1545

[1085] SEQ ID NO 1108 Amino acid sequence of MYH11_1565-1573

[1086] SEQ ID NO 1109 Amino acid sequence of MYH11_ 1597- 1609

[1087] SEQ ID NO 1110 Amino acid sequence of MYH11_1628-1638

[1088] SEQ ID NO 1111 Amino acid sequence of MYH11_ 1666- 1676

[1089] SEQ ID NO 1112 Amino acid sequence of MYH11_ 1684- 1701

[1090] SEQ ID NO 1113 Amino acid sequence of MYH11_1711-1724

[1091] SEQ ID NO 1114 Amino acid sequence of MYH11_1761-1777

[1092] SEQ ID NO 1115 Amino acid sequence of MYH11_1762-1777

[1093] SEQ ID NO 1116 Amino acid sequence of MYH11_1814-1822

[1094] SEQ ID NO 1117 Amino acid sequence of MYH11_1823-1835

[1095] SEQ ID NO 1118 Amino acid sequence of MYH11_1885-1895

[1096] SEQ ID NO 1119 Amino acid sequence of MYH11_19O6-1919

[1097] SEQ ID NO 1120 Amino acid sequence of MYH11_1931-1940

[1098] SEQ ID NO 1121 Amino acid sequence of MYH11_ 1947- 1961

[1099] SEQ ID NO 1122 Amino acid sequence of OXCT1_42-51

[1100] SEQ ID NO 1123 Amino acid sequence of OXCT1_84-104

[1101] SEQ ID NO 1124 Amino acid sequence of OXCT1_111-124

[1102] SEQ ID NO 1125 Amino acid sequence of OXCT1_125-144

[1103] SEQ ID NO 1126 Amino acid sequence of OXCT1_147-173

[1104] SEQ ID NO 1127 Amino acid sequence of OXCT1_177-187

[1105] SEQ ID NO 1128 Amino acid sequence of OXCTl_229-236

[1106] SEQ ID NO 1129 Amino acid sequence of OXCT1_356-368

[1107] SEQ ID NO 1130 Amino acid sequence of OXCT1_369-390

[1108] SEQ ID NO 1131 Amino acid sequence of OXCT1_391-406

[1109] SEQ ID NO 1132 Amino acid sequence of OXCTl_422-434

[1110] SEQ ID NO 1133 Amino acid sequence of OXCTl_456-463

[1111] SEQ ID NO 1134 Amino acid sequence of OXCT1_501-511

[1112] SEQ ID NO 1135 Amino acid sequence of PKP2_15-37

[1113] SEQ ID NO 1136 Amino acid sequence of PKP2_56-66

[1114] SEQ ID NO 1137 Amino acid sequence of PKP2_113-122

[1115] SEQ ID NO 1138 Amino acid sequence of PKP2_148-158

[1116] SEQ ID NO 1139 Amino acid sequence of PKP2_186-193 SEQIDNO: 1140 Amino acid sequence of PKP2_197-204

[1117] SEQIDNO: 1141 Amino acid sequence of PKP2_220-245

[1118] SEQIDNO: 1142 Amino acid sequence of PKP2_273-284

[1119] SEQIDNO: 1143 Amino acid sequence of PKP2_303-315

[1120] SEQIDNO: 1144 Amino acid sequence of PKP2_303-316

[1121] SEQIDNO: 1145 Amino acid sequence of PKP2_316-336

[1122] SEQIDNO: 1146 Amino acid sequence of PKP2_317-336

[1123] SEQIDNO: 1147 Amino acid sequence of PKP2_337-355

[1124] SEQIDNO: 1148 Amino acid sequence of PKP2_356-369

[1125] SEQIDNO: 1149 Amino acid sequence of PKP2_421-430

[1126] SEQIDNO: 1150 Amino acid sequence of PKP2_431-441

[1127] SEQIDNO: 1151 Amino acid sequence of PKP2_564-573

[1128] SEQIDNO: 1152 Amino acid sequence of PKP2_578-591

[1129] SEQIDNO: 1153 Amino acid sequence of PKP2_579-591

[1130] SEQIDNO: 1154 Amino acid sequence of PKP2_592-602

[1131] SEQIDNO: 1155 Amino acid sequence of PKP2_626-635

[1132] SEQIDNO: 1156 Amino acid sequence of PKP2_759-768

[1133] SEQIDNO: 1157 Amino acid sequence of PKP2_812-821

[1134] SEQIDNO: 1158 Amino acid sequence of POSTN_91-115

[1135] SEQIDNO: 1159 Amino acid sequence of POSTN_122-129

[1136] SEQIDNO: 1160 Amino acid sequence of POSTN_130-150

[1137] SEQIDNO: 1161 Amino acid sequence of POSTN_130-151

[1138] SEQIDNO: 1162 Amino acid sequence of POSTN_152-172

[1139] SEQIDNO: 1163 Amino acid sequence of POSTN_152-173

[1140] SEQIDNO: 1164 Amino acid sequence of POSTN_211-228

[1141] SEQIDNO: 1165 Amino acid sequence of POSTN_229-251

[1142] SEQIDNO: 1166 Amino acid sequence of POSTN_252-265

[1143] SEQIDNO: 1167 Amino acid sequence of POSTN_266-281

[1144] SEQIDNO: 1168 Amino acid sequence of POSTN_266-284

[1145] SEQIDNO: 1169 Amino acid sequence of POSTN_290-302

[1146] SEQIDNO: 1170 Amino acid sequence of POSTN_295-302

[1147] SEQIDNO: 1171 Amino acid sequence of POSTN_350-371

[1148] SEQIDNO: 1172 Amino acid sequence of POSTN_372-379

[1149] SEQIDNO: 1173 Amino acid sequence of POSTN_427-435

[1150] SEQIDNO: 1174 Amino acid sequence of POSTN_438-455

[1151] SEQIDNO: 1175 Amino acid sequence of POSTN_482-489 SEQ ID NO 1176 Amino acid sequence of POSTN_490-497

[1152] SEQ ID NO 1177 Amino acid sequence of POSTN_508-522

[1153] SEQ ID NO 1178 Amino acid sequence of POSTN_509-522

[1154] SEQ ID NO 1179 Amino acid sequence of POSTN_523-542

[1155] SEQ ID NO 1180 Amino acid sequence of POSTN_557-575

[1156] SEQ ID NO 1181 Amino acid sequence of POSTN_576-586

[1157] SEQ ID NO 1182 Amino acid sequence of POSTN_611-626

[1158] SEQ ID NO 1183 Amino acid sequence of POSTNJ527-646

[1159] SEQ ID NO 1184 Amino acid sequence of POSTN_663-672

[1160] SEQ ID NO 1185 Amino acid sequence of POSTN_684-694

[1161] SEQ ID NO 1186 Amino acid sequence of POSTN_695-702

[1162] SEQ ID NO 1187 Amino acid sequence of POSTN_703-712

[1163] SEQ ID NO 1188 Amino acid sequence of POSTN_705-712

[1164] SEQ ID NO 1189 Amino acid sequence of POSTN_716-731

[1165] SEQ ID NO 1190 Amino acid sequence of POSTN_716-732

[1166] SEQ ID NO 1191 Amino acid sequence of POSTN_736-747

[1167] SEQ ID NO 1192 Amino acid sequence of POSTN_736-750

[1168] SEQ ID NO 1193 Amino acid sequence of POSTN_754-761

[1169] SEQ ID NO 1194 Amino acid sequence of POSTN_754-764

[1170] SEQ ID NO 1195 Amino acid sequence of POSTN_765-777

[1171] SEQ ID NO 1196 Amino acid sequence of POSTN_765-778

[1172] SEQ ID NO 1197 Amino acid sequence of POSTN_779-786

[1173] SEQ ID NO 1198 Amino acid sequence of POSTN_790-806

[1174] SEQ ID NO 1199 Amino acid sequence of POSTN_807-815

[1175] SEQ ID NO 1200 Amino acid sequence of PRKDC_ 15-24

[1176] SEQ ID NO 1201 Amino acid sequence of PRKDC_25-36

[1177] SEQ ID NO 1202 Amino acid sequence of PRKDC_37-61

[1178] SEQ ID NO 1203 Amino acid sequence of PRKDC_62-70

[1179] SEQ ID NO 1204 Amino acid sequence of PRKDC_100-108

[1180] SEQ ID NO 1205 Amino acid sequence of PRKDC_109-117

[1181] SEQ ID NO 1206 Amino acid sequence of PRKDC_156-163

[1182] SEQ ID NO 1207 Amino acid sequence of PRKDC_217-225

[1183] SEQ ID NO 1208 Amino acid sequence of PRKDC_226-236

[1184] SEQ ID NO 1209 Amino acid sequence of PRKDC_237-246

[1185] SEQ ID NO 1210 Amino acid sequence of PRKDC_247-254

[1186] SEQ ID NO 1211 Amino acid sequence of PRKDC_265-273 SEQ ID NO 1212 Amino acid sequence of PRKDC_311-321

[1187] SEQ ID NO 1213 Amino acid sequence of PRKDC_358-364

[1188] SEQ ID NO 1214 Amino acid sequence of PRKDC_365-374

[1189] SEQ ID NO 1215 Amino acid sequence of PRKDC_380-391

[1190] SEQ ID NO 1216 Amino acid sequence of PRKDC_464-471

[1191] SEQ ID NO 1217 Amino acid sequence of PRKDC_477-489

[1192] SEQ ID NO 1218 Amino acid sequence of PRKDC_526-532

[1193] SEQ ID NO 1219 Amino acid sequence of PRKDC_619-631

[1194] SEQ ID NO 1220 Amino acid sequence of PRKDC_682-689

[1195] SEQ ID NO 1221 Amino acid sequence of PRKDC_701-709

[1196] SEQ ID NO 1222 Amino acid sequence of PRKDC_747-757

[1197] SEQ ID NO 1223 Amino acid sequence of PRKDC_791-801

[1198] SEQ ID NO 1224 Amino acid sequence of PRKDC_811-820

[1199] SEQ ID NO 1225 Amino acid sequence of PRKDC_839-852

[1200] SEQ ID NO 1226 Amino acid sequence of PRKDC_855-868

[1201] SEQ ID NO 1227 Amino acid sequence of PRKDC_869-881

[1202] SEQ ID NO 1228 Amino acid sequence of PRKDC_892-899

[1203] SEQ ID NO 1229 Amino acid sequence of PRKDC_900-913

[1204] SEQ ID NO 1230 Amino acid sequence of PRKDC_914-924

[1205] SEQ ID NO 1231 Amino acid sequence of PRKDC_965-971

[1206] SEQ ID NO 1232 Amino acid sequence of PRKDC_972-981

[1207] SEQ ID NO 1233 Amino acid sequence of PRKDC_ 1063 -1074

[1208] SEQ ID NO 1234 Amino acid sequence of PRKDC_ 1076- 1087

[1209] SEQ ID NO 1235 Amino acid sequence of PRKDC_1187- 1193

[1210] SEQ ID NO 1236 Amino acid sequence of PRKDC_1194- 1202

[1211] SEQ ID NO 1237 Amino acid sequence of PRKDC_ 1203 -1209

[1212] SEQ ID NO 1238 Amino acid sequence of PRKDC_ 1275- 1292

[1213] SEQ ID NO 1239 Amino acid sequence of PRKDC_1312-1321

[1214] SEQ ID NO 1240 Amino acid sequence of PRKDC_1341-1357

[1215] SEQ ID NO 1241 Amino acid sequence of PRKDC_1413-1420

[1216] SEQ ID NO 1242 Amino acid sequence of PRKDC_ 1423 -1445

[1217] SEQ ID NO 1243 Amino acid sequence of PRKDC_1448-1456

[1218] SEQ ID NO 1244 Amino acid sequence of PRKDC_1461-1489

[1219] SEQ ID NO 1245 Amino acid sequence of PRKDC_ 1490- 1497

[1220] SEQ ID NO 1246 Amino acid sequence of PRKDC_1498-1508

[1221] SEQ ID NO 1247 Amino acid sequence of PRKDC_1509-1527 SEQ ID NO 1248 Amino acid sequence of PRKDC_1574-1591

[1222] SEQ ID NO 1249 Amino acid sequence of PRKDC_ 1592- 1606

[1223] SEQ ID NO 1250 Amino acid sequence of PRKDC_ 1643 -1651

[1224] SEQ ID NO 1251 Amino acid sequence of PRKDC_1690-1712

[1225] SEQ ID NO 1252 Amino acid sequence of PRKDC_1713-1727

[1226] SEQ ID NO 1253 Amino acid sequence of PRKDC_1736-1744

[1227] SEQ ID NO 1254 Amino acid sequence of PRKDC_ 1769- 1783

[1228] SEQ ID NO 1255 Amino acid sequence of PRKDC_1788-1806

[1229] SEQ ID NO 1256 Amino acid sequence of PRKDC_1789-1806

[1230] SEQ ID NO 1257 Amino acid sequence of PRKDC_1858-1869

[1231] SEQ ID NO 1258 Amino acid sequence of PRKDC_1876- 1883

[1232] SEQ ID NO 1259 Amino acid sequence of PRKDC_1918-1936

[1233] SEQ ID NO 1260 Amino acid sequence of PRKDC_1974-1985

[1234] SEQ ID NO 1261 Amino acid sequence of PRKDC_1988-2000

[1235] SEQ ID NO 1262 Amino acid sequence of PRKDC_2073-2090

[1236] SEQ ID NO 1263 Amino acid sequence of PRKDC_2091-2102

[1237] SEQ ID NO 1264 Amino acid sequence of PRKDC_2107-2120

[1238] SEQ ID NO 1265 Amino acid sequence of PRKDC_2121-2127

[1239] SEQ ID NO 1266 Amino acid sequence of PRKDC_2133-2143

[1240] SEQ ID NO 1267 Amino acid sequence of PRKDC_2247-2254

[1241] SEQ ID NO 1268 Amino acid sequence of PRKDC_2312-2328

[1242] SEQ ID NO 1269 Amino acid sequence of PRKDC_2314-2328

[1243] SEQ ID NO 1270 Amino acid sequence of PRKDC_2395-2404

[1244] SEQ ID NO 1271 Amino acid sequence of PRKDC_2419-2425

[1245] SEQ ID NO 1272 Amino acid sequence of PRKDC_2434-2441

[1246] SEQ ID NO 1273 Amino acid sequence of PRKDC_2453-2470

[1247] SEQ ID NO 1274 Amino acid sequence of PRKDC_2504-2522

[1248] SEQ ID NO 1275 Amino acid sequence of PRKDC_2531-2538

[1249] SEQ ID NO 1276 Amino acid sequence of PRKDC_2539-2549

[1250] SEQ ID NO 1277 Amino acid sequence of PRKDC_2599-2619

[1251] SEQ ID NO 1278 Amino acid sequence of PRKDC_2620-2628

[1252] SEQ ID NO 1279 Amino acid sequence of PRKDC_2629-2636

[1253] SEQ ID NO 1280 Amino acid sequence of PRKDC_2637-2653

[1254] SEQ ID NO 1281 Amino acid sequence of PRKDC_2654-2683

[1255] SEQ ID NO 1282 Amino acid sequence of PRKDC_2705-2715

[1256] SEQ ID NO 1283 Amino acid sequence of PRKDC_2739-2745 SEQ ID NO 1284 Amino acid sequence of PRKDC_2765-2773

[1257] SEQ ID NO 1285 Amino acid sequence of PRKDC_2777-2786

[1258] SEQ ID NO 1286 Amino acid sequence of PRKDC_2787-2800

[1259] SEQ ID NO 1287 Amino acid sequence of PRKDC_2807-2818

[1260] SEQ ID NO 1288 Amino acid sequence of PRKDC_2836-2842

[1261] SEQ ID NO 1289 Amino acid sequence of PRKDC_2892-2899

[1262] SEQ ID NO 1290 Amino acid sequence of PRKDC_2900-2908

[1263] SEQ ID NO 1291 Amino acid sequence of PRKDC_2900-2909

[1264] SEQ ID NO 1292 Amino acid sequence of PRKDC_2916-2922

[1265] SEQ ID NO 1293 Amino acid sequence of PRKDC_2932-2940

[1266] SEQ ID NO 1294 Amino acid sequence of PRKDC_2941-2950

[1267] SEQ ID NO 1295 Amino acid sequence of PRKDC_2951-2962

[1268] SEQ ID NO 1296 Amino acid sequence of PRKDC_2963-2970

[1269] SEQ ID NO 1297 Amino acid sequence of PRKDC_2971-2978

[1270] SEQ ID NO 1298 Amino acid sequence of PRKDC_3148-3158

[1271] SEQ ID NO 1299 Amino acid sequence of PRKDC_3160-3167

[1272] SEQ ID NO 1300 Amino acid sequence of PRKDC_3173-3186

[1273] SEQ ID NO 1301 Amino acid sequence of PRKDC_3197-3217

[1274] SEQ ID NO 1302 Amino acid sequence of PRKDC_3218-3232

[1275] SEQ ID NO 1303 Amino acid sequence of PRKDC_3290-3302

[1276] SEQ ID NO 1304 Amino acid sequence of PRKDC_33O3-3318

[1277] SEQ ID NO 1305 Amino acid sequence of PRKDC_3325-3335

[1278] SEQ ID NO 1306 Amino acid sequence of PRKDC_3336-3355

[1279] SEQ ID NO 1307 Amino acid sequence of PRKDC_3336-3357

[1280] SEQ ID NO 1308 Amino acid sequence of PRKDC_3358-3372

[1281] SEQ ID NO 1309 Amino acid sequence of PRKDC_3359-3372

[1282] SEQ ID NO 1310 Amino acid sequence of PRKDC_3373-3380

[1283] SEQ ID NO 1311 Amino acid sequence of PRKDC_3468-3474

[1284] SEQ ID NO 1312 Amino acid sequence of PRKDC_3475-3485

[1285] SEQ ID NO 1313 Amino acid sequence of PRKDC_3613-3621

[1286] SEQ ID NO 1314 Amino acid sequence of PRKDC_3697-3708

[1287] SEQ ID NO 1315 Amino acid sequence of PRKDC_3726-3733

[1288] SEQ ID NO 1316 Amino acid sequence of PRKDC_3764-3784

[1289] SEQ ID NO 1317 Amino acid sequence of PRKDC_3790-3799

[1290] SEQ ID NO 1318 Amino acid sequence of PRKDC_38OO-3813

[1291] SEQ ID NO 1319 Amino acid sequence of PRKDC_3814-3825 SEQ ID NO 1320 Amino acid sequence of PRKDC_3826-3833 SEQ ID NO 1321 Amino acid sequence of PRKDC_3865-3872 SEQ ID NO 1322 Amino acid sequence of PRKDC_3890-3901 SEQ ID NO 1323 Amino acid sequence of PRKDC_3966-3975 SEQ ID NO 1324 Amino acid sequence of PRKDC_3993-4007 SEQ ID NO 1325 Amino acid sequence of PRKDC_4051-4070 SEQ ID NO 1326 Amino acid sequence of PRKDC_4091-4105 SEQ ID NO 1327 Amino acid sequence of PRKDC_4106-4119 SEQ ID NO 1328 Amino acid sequence of PTBPl_65-84 SEQ ID NO 1329 Amino acid sequence of PTBPl_66-84 SEQ ID NO 1330 Amino acid sequence of PTBP1_95-122 SEQ ID NO 1331 Amino acid sequence of PTBP1_123-134 SEQ ID NO 1332 Amino acid sequence of PTBP1_135-146 SEQ ID NO 1333 Amino acid sequence of PTBP1_186-2O6 SEQ ID NO 1334 Amino acid sequence of PTBPl_219-238 SEQ ID NO 1335 Amino acid sequence of PTBPl_239-254 SEQ ID NO 1336 Amino acid sequence of PTBPl_352-374 SEQ ID NO 1337 Amino acid sequence of PTBPl_375-392 SEQ ID NO 1338 Amino acid sequence of PTBPl_437-444 SEQ ID NO 1339 Amino acid sequence of PTBPl_455-463 SEQ ID NO 1340 Amino acid sequence of PTBPl_471-497 SEQ ID NO 1341 Amino acid sequence of PTBP1_498-5O8 SEQ ID NO 1342 Amino acid sequence of PTBP1_147-185 SEQ ID NO 1343 Amino acid sequence of PTBP3_65-84 SEQ ID NO 1344 Amino acid sequence of PTBP3_123-134 SEQ ID NO 1345 Amino acid sequence of PTBP3_135-146 SEQ ID NO 1346 Amino acid sequence of PTBP3_138-146 SEQ ID NO 1347 Amino acid sequence of PTBP3_237-252 SEQ ID NO 1348 Amino acid sequence of PTBP3_432-439 SEQ ID NO 1349 Amino acid sequence of PTBP3_450-458 SEQ ID NO 1350 Amino acid sequence of PTBP3_493-503 SEQ ID NO 1351 Amino acid sequence of PTBP3_147-183 SEQ ID NO 1352 Amino acid sequence of RPS4X_38-49 SEQ ID NO 1353 Amino acid sequence of RPS4X_40-49 SEQ ID NO 1354 Amino acid sequence of RPS4X_76-94 SEQ ID NO 1355 Amino acid sequence of RPS4X_78-94 SEQ ID NO: 1356 Amino acid sequence of RPS4X_78-100 SEQ ID NO: 1357 Amino acid sequence of RPS4X_156-168 SEQ ID NO: 1358 Amino acid sequence of RPS4X_169-191 SEQ ID NO: 1359 Amino acid sequence of RPS4X_175-191 SEQ ID NO: 1360 Amino acid sequence of RPS4X_222-230 SEQ ID NO: 1361 Amino acid sequence of RPS4X_231-240 SEQ ID NO: 1362 Amino acid sequence of SIK3_2-25 SEQ ID NO: 1363 Amino acid sequence of STAU 1_159- 168 SEQ ID NO: 1364 Amino acid sequence of STAU1_184-195 SEQ ID NO: 1365 Amino acid sequence of STAU1_197-2O6 SEQ ID NO: 1366 Amino acid sequence of STAUl_220-232 SEQ ID NO: 1367 Amino acid sequence of STAU l_240-250 SEQ ID NO: 1368 Amino acid sequence of STAU l_252-260 SEQ ID NO: 1369 Amino acid sequence of STAU l_302-311 SEQ ID NO: 1370 Amino acid sequence of STAU 1_343 -355 SEQ ID NO: 1371 Amino acid sequence of STAU l_449-457 SEQ ID NO: 1372 Amino acid sequence of STAU l_458-473 SEQ ID NO: 1373 Amino acid sequence of STAUl_552-565 SEQ ID NO: 1374 Amino acid sequence of TNC_58-75 SEQ ID NO: 1375 Amino acid sequence of TNC_76-103 SEQ ID NO: 1376 Amino acid sequence of TNC_110-120 SEQ ID NO: 1377 Amino acid sequence of TNC_126-137 SEQ ID NO: 1378 Amino acid sequence of TNC_155-164 SEQ ID NO: 1379 Amino acid sequence of TNC_628-648 SEQ ID NO: 1380 Amino acid sequence of TNC_649-669 SEQ ID NO: 1381 Amino acid sequence of TNC_670-691 SEQ ID NO: 1382 Amino acid sequence of TNC_692-699 SEQ ID NO: 1383 Amino acid sequence of TNC_692-700 SEQ ID NO: 1384 Amino acid sequence of TNC_700-707 SEQ ID NO: 1385 Amino acid sequence of TNC_708-719 SEQ ID NO: 1386 Amino acid sequence of TNC_708-721 SEQ ID NO: 1387 Amino acid sequence of TNC_748-759 SEQ ID NO: 1388 Amino acid sequence of TNC_752-759 SEQ ID NO: 1389 Amino acid sequence of TNC_763-769 SEQ ID NO: 1390 Amino acid sequence of TNC_770-787 SEQ ID NO: 1391 Amino acid sequence of TNC_803-812 SEQ ID NO: 1392 Amino acid sequence of TNC_813-825 SEQ ID NO: 1393 Amino acid sequence of TNC_826-840 SEQ ID NO: 1394 Amino acid sequence of TNC_847-876 SEQ ID NO: 1395 Amino acid sequence of TNC_877-886 SEQ ID NO: 1396 Amino acid sequence of TNC_878-897 SEQ ID NO: 1397 Amino acid sequence of TNC_887-897 SEQ ID NO: 1398 Amino acid sequence of TNC_901-914 SEQ ID NO: 1399 Amino acid sequence of TNC_902-914 SEQ ID NO: 1400 Amino acid sequence of TNC_927-942 SEQ ID NO: 1401 Amino acid sequence of TNC_950-969 SEQ ID NO: 1402 Amino acid sequence of TNC_970-989 SEQ ID NO: 1403 Amino acid sequence of TNC_973-989 SEQ ID NO: 1404 Amino acid sequence of TNC_1042-1057 SEQ ID NO: 1405 Amino acid sequence of TNC_1069-1091 SEQ ID NO: 1406 Amino acid sequence of TNC_1128-1135 SEQ ID NO: 1407 Amino acid sequence of TNC_1136-1152 SEQ ID NO: 1408 Amino acid sequence of TNC_1153-1182 SEQ ID NO: 1409 Amino acid sequence of TNC_1219-1226 SEQ ID NO: 1410 Amino acid sequence of TNC_1227-1236 SEQ ID NO: 1411 Amino acid sequence of TNC_1310-1317 SEQ ID NO: 1412 Amino acid sequence of TNC_1318-1331 SEQ ID NO: 1413 Amino acid sequence of TNC_1337-1364 SEQ ID NO: 1414 Amino acid sequence of TNC_1401-1414 SEQ ID NO: 1415 Amino acid sequence of TNC_1415-1422 SEQ ID NO: 1416 Amino acid sequence of TNC_1426-1437 SEQ ID NO: 1417 Amino acid sequence of TNC_1492-1516 SEQ ID NO: 1418 Amino acid sequence of TNC_1569-1582 SEQ ID NO: 1419 Amino acid sequence of TNC_1613-1637 SEQ ID NO: 1420 Amino acid sequence of TNC_1638-1653 SEQ ID NO: 1421 Amino acid sequence of TNC_1659-1673 SEQ ID NO: 1422 Amino acid sequence of TNC_ 1660- 1673 SEQ ID NO: 1423 Amino acid sequence of TNC_1674-1681 SEQ ID NO: 1424 Amino acid sequence of TNC_1682-1695 SEQ ID NO: 1425 Amino acid sequence of TNC_1698-1714 SEQ ID NO: 1426 Amino acid sequence of TNC_1699-1714 SEQ ID NO: 1427 Amino acid sequence of TNC_1715-1731 SEQ ID NO: 1428 Amino acid sequence of TNC_1732-1741 SEQ ID NO: 1429 Amino acid sequence of TNC_1742-1761 SEQ ID NO: 1430 Amino acid sequence of TNC_1742-1765 SEQ ID NO: 1431 Amino acid sequence of TNC_1769-1783 SEQ ID NO: 1432 Amino acid sequence of TNC_1819-1837 SEQ ID NO: 1433 Amino acid sequence of TNC_1819-1843 SEQ ID NO: 1434 Amino acid sequence of TNC_1844-1866 SEQ ID NO: 1435 Amino acid sequence of TNC_1883-1891 SEQ ID NO: 1436 Amino acid sequence of TNC_1892-1911 SEQ ID NO: 1437 Amino acid sequence of TNC_1930-1954 SEQ ID NO: 1438 Amino acid sequence of TNC_1955-1963 SEQ ID NO: 1439 Amino acid sequence of TNC_2034-2041 SEQ ID NO: 1440 Amino acid sequence of TNC_2042-2050 SEQ ID NO: 1441 Amino acid sequence of TNC_2051-2063 SEQ ID NO: 1442 Amino acid sequence of TNC_2052-2063 SEQ ID NO: 1443 Amino acid sequence of TNC_2064-2073 SEQ ID NO: 1444 Amino acid sequence of TNC_2078-2089 SEQ ID NO: 1445 Amino acid sequence of TNC_2103-2120 SEQ ID NO: 1446 Amino acid sequence of TNC_2121-2127 SEQ ID NO: 1447 Amino acid sequence of TNC_2174-2185

[1292] Detailed description

[1293] General Techniques and Definitions

[1294] Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (e.g. in genomics, immunology, molecular biology, proteomics, immunohistochemistry, biochemistry, oncology, and pharmacology).

[1295] The present disclosure is performed using, unless otherwise indicated, conventional techniques of molecular biology, proteomics, microbiology, recombinant DNA technology and immunology. Such procedures are described, for example, in Principles of Proteomics (Moore, Ian, 2016); Current Protocols in Protein Science (Edited by Coligan et al., 1995); Proteomics in Systems Biology; Reinders, J., Ed.; Methods in Molecular Biology; Springer New York: New York, NY, 2016; Vol. 1394; Quantitative Methods in Proteomics; Eisenacher et al. Eds.; Methods in Molecular Biology; Springer US: New York, NY, 2021; Vol. 2228; Shotgun Proteomics: Methods and Protocols; Carrera, M., Mateos, J., Eds., Methods in Molecular Biology; Springer US: New York, NY, 2021; Vol. 2259; Advancements of Mass Spectrometry in Biomedical Research; Woods, A. G., Darie, C. C., Eds., Advances in Experimental Medicine and Biology; Springer International Publishing: Cham, 2019; Vol. 1140; Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, New York, Fourth Edition (2012), whole of Vols I, II, and III; DNA Cloning: A Practical Approach, Vols. I and II (D. N. Glover, Second Edition., 1995), IRL Press, Oxford, whole of text; Oligonucleotide Synthesis: A Practical Approach (M. J. Gait, ed, 1984) IRL Press, Oxford, whole of text, and particularly the papers therein by Gait, ppl-22; Atkinson et al, pp35-81; Sproat et al, pp 83-115; and Wu et al, pp 135-151; 4. Nucleic Acid Hybridization: A Practical Approach (B. D. Hames & S. J. Higgins, eds., 1985) IRL Press, Oxford, whole of text; Immobilized Cells and Enzymes: A Practical Approach (1986) IRL Press, Oxford, whole of text; Perbal, B., A Practical Guide to Molecular Cloning (1984) and Methods In Enzymology (S. Colowick and N. Kaplan, eds., Academic Press, Inc.), whole of series.

[1296] Those skilled in the art will appreciate that the present disclosure is susceptible to variations and modifications other than those specifically described. It is to be understood that the disclosure includes all such variations and modifications. The disclosure also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features.

[1297] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purpose of exemplification only. Functionally equivalent products, compositions and methods are clearly within the scope of the disclosure, as described herein.

[1298] Each feature of any particular aspect or embodiment of the present disclosure may be applied mutatis mutandis to any other aspect or embodiment of the present disclosure.

[1299] Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, composition of matter, group of steps or group of compositions of matter shall be taken to encompass one and a plurality (i.e. one or more) of those steps, compositions of matter, groups of steps or group of compositions of matter.

[1300] As used herein, the singular forms of “a”, “and” and “the” include plural forms of these words, unless the context clearly dictates otherwise.

[1301] The term “and / or”, e.g., “X and / or Y” shall be understood to mean either “X and Y” or “X or Y” and shall be taken to provide explicit support for both meanings or for either meaning.

[1302] Throughout the present specification, various aspects and components of the disclosure can be presented in a range format. The range format is included for convenience and should not be interpreted as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub- ranges as well as individual numerical values within that range, unless specifically indicated. For example, description of a range such as from 1 to 5 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 5, from 3 to 5 etc., as well as individual and partial numbers within the recited range, for example, 1, 2, 3, 4, 5, 5.5 and 6, unless where integers are required or implicit from context. This applies regardless of the breadth of the disclosed range. Where specific values are required, these will be indicated in the specification.

[1303] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[1304] It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[1305] As used herein, the terms “approximately” and “about” refer to tolerances or variances associated with numerical values recited herein (e.g., ± 0.1%, 0.5%, 1.0%, 5.0% or 10%). The extent of such tolerances and variances are well understood by persons skilled in the art. Typically, such tolerances and variances do not compromise the structure, function and / or implementation of the compositions and methods described herein.

[1306] All computer programs, algorithms, patent and scientific literature referred to herein is incorporated herein by reference. For the present disclosure, the database accession number or unique identifier provided herein for a gene or protein, as well as the gene and / or protein sequence or sequences associated therewith, are incorporated by reference herein.

[1307] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each of the appended claims.

[1308] Methods of determining a prognosis

[1309] The inventors have surprisingly shown for the first time that the expression level of proteins from a protein-based signature or a peptide -based signature in a pre-treatment biopsy correlates with the severity and disease progression of oropharyngeal cancer, such as HPV-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC), in patients following treatment (e.g., following surgical resection of the cancer). Advantageously, such a method may allow a physician to determine the severity or aggressiveness of an oropharyngeal cancer in a subject and to make appropriate, informed, and timely treatment decisions based on this information.

[1310] Accordingly, the inventors have developed methods of determining a prognosis for oropharyngeal cancer.

[1311] As such, in one broad form, the present disclosure provides a method of determining: (a) a prognosis for a subject with an oropharyngeal cancer; and / or (b) the aggressiveness of an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, ACTB, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, ATP5F1B, ATP5F1D, BORCS6, CDKN2A, CDS2, CNDP2, COL8A1, CTSZ, DARS2, DECR1, DOK3, EMILIN1, ENO1, EPPK1, ERP29, ETHE1, FN1, FNBP1, GAPVD1, GARS1, GNAI3, GNL1, GOLGA3, GSR, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, IGKV1-6, ITIH2, IVL, KRT17, KRT6C, LAP3, LMNB1, MGST2, MMP2, MUC5B, MVP, MYH11, NOP56, OPA3, OXCT1, PKP2, POSTN, PRKDC, PSMB4, PSMG1, PTBP1, PTBP3, RPS4X, S100A4, SIK3, SPRR3, STAG1, STAU1, TAP2, TCEA1, TNC, UGDH and WDR81, or a fragment, variant or derivative thereof, to thereby determine the prognosis and / or the aggressiveness of the oropharyngeal cancer in the subject.

[1312] In a related broad form, the present disclosure provides a method of determining: (a) a prognosis for a subject with an oropharyngeal cancer; and / or (b) the aggressiveness of an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, BORCS6, CDS2, CNDP2, COL8A1, CTSZ, DECR1, DOK3, ERP29, ETHE1, FNBP1, GAPVD1, GARS1, GOLGA3, GSTO1, HAPLN3, HLA-A, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, KRT17, LAP3, LMNB1, MGST2, MMP2, MVP, NOP56, OPA3, PSMB4, PSMG1, S100A4, SPRR3, STAG1, TAP2, TCEA1, UGDH and WDR81, or a fragment, variant or derivative thereof, to thereby determine the prognosis and / or the aggressiveness of the oropharyngeal cancer in the subject.

[1313] In another broad form, the present disclosure provides a method of determining: (a) a prognosis for a subject with an oropharyngeal cancer; and / or (b) the aggressiveness of an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA- A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1, WDR81, ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, to thereby determine the prognosis and / or the aggressiveness of the oropharyngeal cancer in the subject.

[1314] In one particular form, the present disclosure provides a method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA- DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

[1315] In another form, the present disclosure provides a method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

[1316] In a further form, the present disclosure provides a method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject. In a related form, the present disclosure provides a method of determining the aggressiveness of an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, to thereby determine the aggressiveness of the oropharyngeal cancer in the subject.

[1317] In a further form, the present disclosure provides a method of determining the aggressiveness of an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, to thereby determine the aggressiveness of the oropharyngeal cancer in the subject.

[1318] In another form, the present disclosure provides a method of determining the aggressiveness of an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, to thereby determine the aggressiveness of the oropharyngeal cancer in the subject.

[1319] With respect to the aspects described herein, the term “subject” includes, but is not limited to, mammals, inclusive of humans, performance animals (such as horses, camels, greyhounds), livestock (such as cows, sheep, horses) and companion animals (such as cats and dogs). In one example, the subject is a human, such as a male human or a female human.

[1320] As generally used herein, the terms “cancer”, “tumour”, “malignant” and “malignancy” refer to diseases or conditions, or to cells or tissues associated with the diseases or conditions, characterized by aberrant or abnormal cell proliferation, differentiation and / or migration often accompanied by an aberrant or abnormal molecular phenotype that includes one or more genetic mutations or other genetic changes associated with oncogenesis, expression of tumour markers, loss of tumour suppressor expression or activity and / or aberrant or abnormal cell surface marker expression.

[1321] The term “oropharyngeal cancer” as used herein, refers to cancers derived from oral cavity, pharynx, larynx or upper oesophagus. At an early stage of the oropharyngeal cancer, the tissue of origin may be more readily determined. Oropharyngeal cancer, however, is typically identified at a late invasive stage such that the tissue of origin cannot be determined. Therefore, cancers arising from these sources are collectively termed “oropharyngeal cancer”.

[1322] Suitably, the oropharyngeal cancer is or comprises oropharyngeal squamous cell cancer (OPSCC). Oropharyngeal squamous cell cancer is a type of head and neck cancer that occurs in the oropharynx, the middle part of the throat that includes the soft palate, the base of the tongue, the tonsils and the side and back wall of the throat. In some examples, the oropharyngeal cancer is or comprises Human papillomavirus(HPV)-positive oropharyngeal squamous cell cancer (HPV+OPSCC). An oral infection with HPV typically precedes the development of HPV+OPSCC. Squamous cell cancers of the tonsils are more strongly associated with HPV infection than are cancers of other regions of the head and neck. HPV+OPSCC is a subtype of oropharyngeal squamous cell cancer, in which more than 95% of cancers are associated with the HPV type 16. Accordingly, the subject may suffer from HPV16-positive OPSCC.

[1323] The terms “prognosis” and “prognostic” are used herein to include making a prognosis, which can provide for predicting a clinical outcome (with or without medical treatment), selecting an appropriate course of treatment (or whether treatment would be effective) and / or monitoring a current treatment and potentially changing the treatment. This may be at least partly based on determining an expression level of the one or more protein biomarkers by the methods of the present disclosure, which may be in combination with determining: (a) the expression and / or activity levels of one or more additional protein and / or other nucleic acid biomarkers; and / or (b) one or more clinical variables, such as TNM classification or staging (i.e., T describes the size of the tumour and any spread of cancer into nearby tissue; N describes the spread of the cancer to nearby lymph nodes; and M describes metastasis) and smoking exposure (e.g., pack / years). A prognosis may also include a prediction, forecast or anticipation of any lasting or permanent physical or psychological effects of oropharyngeal cancer suffered by the subject after the oropharyngeal cancer has been successfully treated or otherwise resolved. Furthermore, a prognosis may include one or more of determining disease progression potential or occurrence (e.g., cancer aggressiveness, metastasis), therapeutic responsiveness, implementing appropriate treatment regimes, determining the probability, likelihood or potential for oropharyngeal cancer recurrence after therapy, likelihood of survival for a particular period of time (e.g., 1, 2, 5 or 10 years) after diagnosis or treatment and prediction of development of resistance to established therapies. A positive prognosis typically refers to a beneficial clinical outcome or outlook, such as long-term survival without recurrence of the subject's oropharyngeal cancer, whereas a negative prognosis typically refers to a negative clinical outcome or outlook, such as oropharyngeal cancer resistance to treatment, recurrence, progression and / or metastasis.

[1324] Suitably, if the expression level of said one or more protein biomarkers is altered or modulated in the one or plurality of cancer cells, tissues or organs, the prognosis may be negative or positive. In one example, an increased level of expression of a first subset of the one or more protein biomarkers and / or a decreased level of expression of a second subset of the one or more protein biomarkers indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer (e.g., a less aggressive oropharyngeal cancer). In a related example, a decreased level of expression of a first subset of the one or more protein biomarkers and / or an increased level of expression of a second subset of the one or more protein biomarkers indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer (e.g., a more aggressive oropharyngeal cancer).

[1325] In various examples of the present methods, a decreased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer. Conversely, an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, suitably indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer.

[1326] In some examples of the present methods, an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer. Conversely, a decreased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, G0LGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, suitably indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer.

[1327] In various examples of the present methods, a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer. Conversely, an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4, and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer.

[1328] In some examples of the present methods, an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer. Conversely, a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4, and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer.

[1329] In certain examples of the present methods, a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer. Conversely, an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer.

[1330] In various examples of the present methods, an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with a more favourable or positive prognosis for the subject’s oropharyngeal cancer. Conversely, a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with a less favourable or negative prognosis for the subject’s oropharyngeal cancer.

[1331] The present method is also useful for determining, for example, the risk of an event occurring, or the timing to an event occurring. For example, the present prognostic methods are useful for determining the risk of patient’s oropharyngeal cancer recurring (e.g., after surgical resection thereof), determining the risk of a patient dying early as a result of oropharyngeal cancer e.g., as a result of HPV-positive OPSCC, or determining the risk of metastasis or the timing to metastasis.

[1332] Such methods are also applicable to determining, for example, the risk of or time to development of one or more of the following:

[1333] (i) onset of clinical oropharyngeal cancer;

[1334] (ii) the progression, recurrence or metastasis of oropharyngeal cancer, such as after administration of an anti-cancer treatment and / or surgical resection; and

[1335] (iii) the likelihood of response (e.g., a complete response, a partial response or stable disease) of a subject to a therapeutic or prophylactic agent.

[1336] In some examples, the present method includes determining whether the subject has a low, intermediate or high risk of: (a) progression, recurrence or metastasis of the oropharyngeal cancer; and / or (b) dying, within a particular time frame, such as 1, 2, 5 or 10 years.

[1337] The term “low risk” in regards to tumours or to patients diagnosed with cancer refers to a tumour or patient with a lower probability (e.g., less than about a 25%, 20%, 15%, 10% or 5% probability, likelihood or chance) of metastasis, disease progression or disease recurrence and / or a lower probability (e.g., less than about a 25%, 20%, 15%, 10% or 5% probability, likelihood or chance) of causing death or dying within a particular time frame, such as within about five years of first diagnosis or testing, than all the tumours or patients within a given population. The term “low risk” may also refer to a tumour or patient with a higher probability (e.g., greater than about a 70%, 75%, 80%, 85%, 90% or 95% probability, likelihood or chance) of at least partly responding, such as a complete or partial response, to an anti-cancer treatment, such as those described herein.

[1338] The term “high risk” in regards to tumours or to patients diagnosed with cancer refers to a tumour or patient with a higher probability (e.g., greater than about a 70%, 75%, 80%, 85%, 90% or 95% probability, likelihood or chance) of metastasis, disease progression or disease recurrence and / or higher probability (e.g., greater than about a 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% probability, likelihood or chance) of causing death or dying within a particular time frame, such as within about five years of first diagnosis or testing, than all the tumours or patients within a given population. The term “high risk” may also refer to a tumour or patient with a higher probability (e.g., greater than about a 70%, 75%, 80%, 85%, 90% or 95% probability, likelihood or chance) of substantially not or minimally responding (e.g., the cancer being at least partially resistant) to an anti-cancer treatment, such as those described herein.

[1339] The term “intermediate risk” in regards to tumours or to patients diagnosed with cancer refers to a tumour or patient with an intermediate probability (e.g., a probability, likelihood or chance of between about 25% to about 70%, such as 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or any range therein) of metastasis, disease progression or disease recurrence and / or higher probability (e.g., a probability, likelihood or chance of between about 25% to about 50%, such as 25%, 30%, 35%, 40%, 45%, 50% or any range therein) of causing death or dying within a particular time frame, such as within about five years of first diagnosis or testing, than all the tumours or patients within a given population. The term “intermediate risk” may also refer to a tumour or patient with an intermediate probability (e.g., a probability, likelihood or chance of between about 25% to about 70%, such as 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70% or any range therein) of at least partly responding or not responding to an anti-cancer treatment, such as those described herein.

[1340] In one example, the prognosis may be used, at least in part, to determine whether the subject would benefit from treatment of the oropharyngeal cancer, such as with those anti-cancer agents described herein. In another example, the prognosis may be used, at least in part, to develop a treatment strategy for the subject. The methods disclosed herein may further comprise determining the suitability of the subject for a treatment, such as those hereinafter described, based, at least in part, on the prognosis. By “aggressiveness” and “aggressive” is meant a property or propensity for a cancer to have a relatively poor prognosis due to one or more of a combination of features or factors including: at least partial resistance to therapies available for cancer treatment; invasiveness; metastatic potential; recurrence after treatment; and a low probability of patient survival, although without limitation thereto.

[1341] A level of expression of the one or more protein biomarkers, or a risk score derived therefrom, can indicate or correlate with a level of aggressiveness of the oropharyngeal cancer. For example, the higher the risk score calculated from the expression level of the one or more protein biomarkers, the more severe or aggressive the oropharyngeal cancer. In alternative examples, the lower the risk score calculated from the expression level of the one or more protein biomarkers, the more severe or aggressive the oropharyngeal cancer. Thus, the methods disclosed herein may further comprise determining a disease stage and / or grade for the subject’s oropharyngeal cancer based on, at least in part, the level of expression of the one or more protein biomarkers, or a risk score derived therefrom.

[1342] The term “survival” as used herein refers to survival of a subject having oropharyngeal cancer for a particular period of time, such as at least 1 year (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 etc years), more particularly 2 years, even more particularly 3 years, yet even more particularly 5 years, or still even more particularly 10 years from the time of diagnosis or prognosis. For example, the term “survival” may refer to survival for at least 1 year, or at least 2 years, or at least 3 years, or at least 5 years, or for at least 10 years from the time of diagnosis or prognosis. In another example, the term “survival” may refer to survival of a subject having oropharyngeal cancer for a particular period of time, such as at least 1 year, or at least 2 years, or at least 3 years, or at least 5 years, or at least 10 years following surgery and / or other treatment, such as CRT, associated with oropharyngeal cancer.

[1343] Methods of treatment and predicting responsiveness to treatment

[1344] Further to the above, the methods described herein may improve patient outcomes by identifying subjects who are likely to fail standard therapy, such as CRT, and who could potentially benefit from alternative or targeted treatments.

[1345] Accordingly, the inventors have developed methods of: (a) treating an oropharyngeal cancer; and (b) predicting responsiveness of an oropharyngeal cancer to a treatment.

[1346] In one broad form, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, ACTB, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, ATP5F1B, ATP5F1D, BORCS6, CDKN2A, CDS2, CNDP2, COL8A1, CTSZ, DARS2, DECR1, DOK3, EMILIN1, ENO1, EPPK1, ERP29, ETHE1, FN1, FNBP1, GAPVD1, GARS1, GNAI3, GNL1, GOLGA3, GSR, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, IGKV1-6, ITIH2, IVL, KRT17, KRT6C, LAP3, LMNB1, MGST2, MMP2, MUC5B, MVP, MYH11, NOP56, OPA3, OXCT1, PKP2, POSTN, PRKDC, PSMB4, PSMG1, PTBP1, PTBP3, RPS4X, S100A4, SIK3, SPRR3, STAG1, STAU1, TAP2, TCEA1, TNC, UGDH and WDR81, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level or likelihood of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[1347] In another broad form, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, BORCS6, CDS2, CNDP2, COL8A1, CTSZ, DECR1, D0K3, ERP29, ETHE1, FNBP1, GAPVD1, GARS1, GOLGA3, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, KRT17, LAP3, LMNB1, MGST2, MMP2, MVP, NOP56, OPA3, PSMB4, PSMG1, S100A4, SPRR3, STAG1, TAP2, TCEA1, UGDH and WDR81, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level or likelihood of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[1348] In a particular form, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level or likelihood of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment. In another form, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level or likelihood of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[1349] In a further form, the present disclosure provides a method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level or likelihood of responsiveness, such as increased or decreased responsiveness, of the oropharyngeal cancer to the treatment.

[1350] In view of the above, the present methods may further include the step of treating the cancer in the subject. By way of example, this can include administering to the subject a therapeutically effective amount of the treatment, such as those described herein (e.g., CRT), when the expression level of the one or more protein biomarkers and / or the risk score indicates or correlates with relatively increased responsiveness or a relatively increased level of responsiveness (e.g., an increased level of predicted responsiveness) of the oropharyngeal cancer to the treatment. In such examples, the therapeutically effective amount of the treatment may comprise a reduced or low dose of the treatment, such as a reduced or low dose of CRT. To this end, the subject may be determined to be in a low risk or intermediate risk group based on the expression level of the one or more protein biomarkers. In such examples, the subject may alternatively not be administered a treatment for their oropharyngeal cancer, as described in more detail herein.

[1351] In certain examples of the present methods, a decreased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, indicates or correlates with relatively increased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Conversely, an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, suitably indicates or correlates with relatively decreased responsiveness of the oropharyngeal cancer to the treatment, such as CRT.

[1352] In some examples of the present methods, an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, indicates or correlates with relatively increased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Conversely, a decreased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, suitably indicates or correlates with relatively decreased responsiveness of the oropharyngeal cancer to the treatment, such as CRT.

[1353] In some examples of the present methods, a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB 1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with relatively increased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Conversely, an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB 1, MMP2, S 100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with relatively decreased responsiveness of the oropharyngeal cancer to the treatment, such as CRT.

[1354] In some examples of the present methods, an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with relatively increased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Conversely, a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with relatively decreased responsiveness of the oropharyngeal cancer to the treatment, such as CRT.

[1355] In particular examples of the present methods, a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with relatively increased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Conversely, an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with relatively decreased responsiveness of the oropharyngeal cancer to the treatment, such as CRT.

[1356] In some examples of the present methods, an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with relatively increased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Conversely, a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with relatively decreased responsiveness of the oropharyngeal cancer to the treatment, such as CRT. Alternatively, the present method can include refraining from administering a first treatment, discontinuing administration of a first treatment, administering a high dose of a first treatment and / or administering a second treatment to the subject, such as when the expression level of the one or more protein biomarkers and / or a risk score derived therefrom indicates or correlates with relatively reduced responsiveness or resistance of the oropharyngeal cancer to said first treatment, and more particularly CRT. In such examples, the subject may be determined to be in a high risk or intermediate risk group based on the expression level of the one or more protein biomarkers. Moreover, the first treatment is suitably different from that of the second treatment.

[1357] Accordingly, in instances when a decreased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject, which is indicative of a relatively decreased responsiveness of the oropharyngeal cancer to a first treatment (e.g., CRT), the present method may include the further step or steps of refraining from administering the first treatment, discontinuing administration of a first treatment, administering a high dose of the first treatment and / or administering a second treatment to the subject.

[1358] Conversely, in instances when an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject, which is indicative of a relatively decreased responsiveness of the oropharyngeal cancer to a first treatment (e.g., CRT), the present method may include the further step or steps of refraining from administering the first treatment, discontinuing administration of a first treatment, administering a high dose of the first treatment and / or administering a second treatment to the subject.

[1359] Furthermore, in instances when a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject, which is indicative of a relatively decreased responsiveness of the oropharyngeal cancer to a first treatment (e.g., CRT), the present method may include the further step or steps of refraining from administering the first treatment, discontinuing administration of a first treatment, administering a high dose of the first treatment and / or administering a second treatment to the subject.

[1360] Conversely, in instances when an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject, which is indicative of a relatively decreased responsiveness of the oropharyngeal cancer to a first treatment (e.g., CRT), the present method may include the further step or steps of refraining from administering the first treatment, discontinuing administration of a first treatment, administering a high dose of the first treatment and / or administering a second treatment to the subject.

[1361] Moreover, in instances when a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject, which is indicative of a relatively decreased responsiveness of the oropharyngeal cancer to a first treatment (e.g., CRT), the present method may include the further step or steps of refraining from administering the first treatment, discontinuing administration of a first treatment, administering a high dose of the first treatment and / or administering a second treatment to the subject.

[1362] Conversely, in instances when an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject, which is indicative of a relatively decreased responsiveness of the oropharyngeal cancer to a first treatment (e.g., CRT), the present method may include the further step or steps of refraining from administering the first treatment, discontinuing administration of a first treatment, administering a high dose of the first treatment and / or administering a second treatment to the subject.

[1363] In a related broad form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, ACTB, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, ATP5F1B, ATP5F1D, BORCS6, CDKN2A, CDS2, CNDP2, COL8A1, CTSZ, DARS2, DECR1, DOK3, EMILIN1, ENO1, EPPK1, ERP29, ETHE1, FN1, FNBP1, GAPVD1, GARS1, GNAI3, GNL1, GOLGA3, GSR, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, IGKV1-6, ITIH2, IVL, KRT17, KRT6C, LAP3, LMNB1, MGST2, MMP2, MUC5B, MVP, MYH11, NOP56, OPA3, OXCT1, PKP2, POSTN, PRKDC, PSMB4, PSMG1, PTBP1, PTBP3, RPS4X, S100A4, SIK3, SPRR3, STAG1, STAU1, TAP2, TCEA1, TNC, UGDH and WDR81, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[1364] In a further related broad form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, BORCS6, CDS2, CNDP2, COL8A1, CTSZ, DECR1, DOK3, ERP29, ETHE1, FNBP1, GAPVD1, GARS1, GOLGA3, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, KRT17, LAP3, LMNB1, MGST2, MMP2, MVP, NOP56, OPA3, PSMB4, PSMG1, S100A4, SPRR3, STAG1, TAP2, TCEA1, UGDH and WDR81, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[1365] In a particular form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA- DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[1366] Generally, an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, suitably indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment, such as CRT. Alternatively, a decreased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, suitably indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment, such as CRT.

[1367] In another form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[1368] Suitably, an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment, such as CRT. In alternative examples, a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment, such as CRT.

[1369] In a further form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of a phosphorylated form of one or more protein biomarkers has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

[1370] Suitably, an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment, such as CRT. In alternative examples, a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment, such as CRT.

[1371] In a broad form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, ACTB, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, ATP5F1B, ATP5F1D, BORCS6, CDKN2A, CDS2, CNDP2, COL8A1, CTSZ, DARS2, DECR1, DOK3, EMILIN1, ENO1, EPPK1, ERP29, ETHE1, FN1, FNBP1, GAPVD1, GARS1, GNAI3, GNL1, GOLGA3, GSR, GSTO1, HAPLN3, HLA-A, HLA- DPA1, HLA-DRB4, IGHM, IGKV1-6, ITIH2, IVL, KRT17, KRT6C, LAP3, LMNB1, MGST2, MMP2, MUC5B, MVP, MYH11, NOP56, OPA3, OXCT1, PKP2, POSTN, PRKDC, PSMB4, 1

[1372] PSMG1, PTBP1, PTBP3, RPS4X, S100A4, SIK3, SPRR3, STAG1, STAU1, TAP2, TCEA1, TNC, UGDH and WDR81, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[1373] In another broad form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, BORCS6, CDS2, CNDP2, COL8A1, CTSZ, DECR1, DOK3, ERP29, ETHE1, FNBP1, GAPVD1, GARS1, GOLGA3, GSTO1, HAPLN3, HLA-A, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, KRT17, LAP3, LMNB1, MGST2, MMP2, MVP, NOP56, OPA3, PSMB4, PSMG1, S100A4, SPRR3, STAG1, TAP2, TCEA1, UGDH and WDR81, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[1374] In a certain form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[1375] In another form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[1376] In a further form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

[1377] In one broad form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of one or more protein biomarkers selected from the group consisting of ACP2, ACTB, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, ATP5F1B, ATP5F1D, BORCS6, CDKN2A, CDS2, CNDP2, COL8A1, CTSZ, DARS2, DECR1, DOK3, EMILIN1, ENO1, EPPK1, ERP29, ETHE1, FN1, FNBP1, GAPVD1, GARS1, GNAI3, GNL1, GOLGA3, GSR, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, IGKV1-6, ITIH2, IVL, KRT17, KRT6C, LAP3, LMNB1, MGST2, MMP2, MUC5B, MVP, MYH11, NOP56, OPA3, OXCT1, PKP2, POSTN, PRKDC, PSMB4, PSMG1, PTBP1, PTBP3, RPS4X, S100A4, SIK3, SPRR3, STAG1, STAU1, TAP2, TCEA1, TNC, UGDH and WDR81, or a fragment, variant or derivative thereof, has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[1378] In a further broad form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of one or more protein biomarkers selected from the group consisting of ACP2, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, BORCS6, CDS2, CNDP2, COL8A1, CTSZ, DECR1, DOK3, ERP29, ETHE1, FNBP1, GAPVD1, GARS1, GOLGA3, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, KRT17, LAP3, LMNB1, MGST2, MMP2, MVP, NOP56, OPA3, PSMB4, PSMG1, S100A4, SPRR3, STAG1, TAP2, TCEA1, UGDH and WDR81, or a fragment, variant or derivative thereof, has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment. In a particular form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of one or more protein biomarkers selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, has been determined in a biological sample, such as a biological sample comprising one or a plurality of cancer cells, tissues or organs, obtained from the subject and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[1379] Accordingly, the treatment for the oropharyngeal cancer is suitably administered to the subject in instances when an increased expression level of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or a decreased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject. Alternatively, the treatment for the oropharyngeal cancer is suitably administered to the subject in instances when a decreased expression level of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, GSTO1, HLA-DPA1, HLA-DRB4, IGHM, MGST2, STAG1 and / or TAP2, or a fragment, variant or derivative thereof, and / or an increased expression level of FNBP1, GOLGA3, ITIH2, HAPLN3, IVL, PSMG1 and / or UGDH, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject.

[1380] In another form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of one or more protein biomarkers selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA- A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, has been determined and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[1381] Accordingly, the treatment for the oropharyngeal cancer is suitably administered to the subject in instances when an increased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or a decreased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB 1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject. In alternative examples, the treatment for the oropharyngeal cancer is suitably administered to the subject in Instances when a decreased expression level of ARL6IP5, CDS2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, LAP3, LMNB1, OPA3, MVP, NOP56, PSMB4, STAG1, TCEA1 and / or WDR81, or a fragment, variant or derivative thereof, and / or an increased expression level of AGRN, ALDOA, ATP2A2, CNDP2, DECR1, KRT17, LAP3, LMNB1, MMP2, S100A4 and / or SPRR3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject.

[1382] In a further form, the present disclosure provides a method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which a level of expression of a phosphorylated form of one or more protein biomarkers selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof has been determined and is indicative of the oropharyngeal cancer being at least partly responsive to the treatment.

[1383] Accordingly, the treatment for the oropharyngeal cancer is suitably administered to the subject in instances when an increased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or a decreased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject. In alternative examples, the treatment for the oropharyngeal cancer is suitably administered to the subject in instances when a decreased expression level of ACTB, ATP5F1B, EMILIN1, EPPK1, GNAI3, GNL1, GSR, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, STAU1 and / or TNC, or a fragment, variant or derivative thereof, and / or an increased expression level of ATP5F1D, CDKN2A, DARS2, ENO1, FN1, IGKV1-6, KRT6C and / or SIK3, or a fragment, variant or derivative thereof, is determined in the one or plurality of cancer cells, tissues or organs obtained from the subject.

[1384] Suitably, for the present methods, a risk score has been determined using the expression level of the one or more protein biomarkers and the risk score is indicative of the oropharyngeal cancer being at least partly responsive to the treatment. In such examples, the subject may be further classified, such as low risk, intermediate risk or high risk, or more particularly low risk or high risk, based on the risk score.

[1385] As used herein, the term “therapeutically effective amount” describes a quantity of a specified agent (e.g., an anti-cancer agent) or treatment, such as chemotherapy, radiation therapy, a molecularly targeted therapy and / or immunotherapy, sufficient to achieve a desired effect in a subject being treated with that agent. For example, this can be the amount of a composition comprising one or more agents that are necessary to reduce, alleviate and / or prevent a cancer or cancer associated disease, disorder or condition. In some examples, a “therapeutically effective amount” is sufficient to reduce or eliminate a symptom of a cancer. In other examples, a “therapeutically effective amount” is an amount sufficient to achieve a desired biological effect, for example an amount that is effective to decrease or prevent cancer growth, recurrence, progression and / or metastasis.

[1386] Ideally, a therapeutically effective amount of an agent is an amount sufficient to induce the desired result without causing a substantial cytotoxic effect in the subject. The effective amount of an agent useful for reducing, alleviating and / or preventing a cancer will be dependent on the subject being treated, the type and severity of any associated disease, disorder and / or condition (e.g., the number and location of any associated metastases), and the manner of administration of the therapeutic composition. As described in more detail below, a “therapeutically effective amount” also includes a low or reduced dose and a high or increased dose of an anti-cancer agent or treatment when compared to a standard therapeutic dose thereof.

[1387] Suitably, the various agents, anti-cancer agents or cancer treatments described herein are administered to a subject as a pharmaceutical composition comprising a pharmaceutically - acceptable carrier, diluent or excipient. In this regard, any dosage form and route of administration, such as those provided therein, may be employed for providing a subject with the composition of the present disclosure.

[1388] By “pharmaceutically-acceptable carrier, diluent or excipient” is meant a solid or liquid filler, diluent or encapsulating substance that may be safely used in systemic administration. Depending upon the particular route of administration, a variety of carriers, well known in the art may be used. These carriers may be selected from a group including sugars, starches, cellulose and its derivatives, malt, gelatine, talc, calcium sulfate, liposomes and other lipid-based carriers, vegetable oils, synthetic oils, polyols, alginic acid, phosphate buffered solutions, emulsifiers, isotonic saline and salts such as mineral acid salts including hydrochlorides, bromides and sulfates, organic acids such as acetates, propionates and malonates and pyrogen-free water.

[1389] Useful references describing pharmaceutically acceptable carriers, diluents and excipients include Remington’s Pharmaceutical Sciences (Mack Publishing Co. N.J. USA, 1991) and Handbook of Pharmaceutical Excipients - Ninth Edition (Edited by Paul J Sheskey, Bruno C Hancock, Gary P Moss, David J Goldfarb; Pharmaceutical Press, 2020), which are incorporated herein by reference.

[1390] Any safe route of administration may be employed for providing a patient with the composition of the present disclosure. For example, oral, rectal, parenteral, sublingual, buccal, intravenous, intra-articular, intra-muscular, intra-dermal, subcutaneous, inhalational, intraocular, intraperitoneal, intracerebroventricular, transdermal and the like may be employed.

[1391] Dosage forms include tablets, dispersions, suspensions, injections, solutions, syrups, troches, capsules, suppositories, aerosols, transdermal patches and the like. These dosage forms may also include injecting or implanting controlled releasing devices designed specifically for this purpose or other forms of implants modified to act additionally in this fashion. Controlled release of the therapeutic agent may be effected by coating the same, for example, with hydrophobic polymers including acrylic resins, waxes, higher aliphatic alcohols, polylactic and polyglycolic acids and certain cellulose derivatives such as hydroxypropylmethyl cellulose. In addition, the controlled release may be effected by using other polymer matrices, liposomes and / or microspheres.

[1392] Compositions of the present disclosure suitable for oral or parenteral administration may be presented as discrete units such as capsules, sachets or tablets each containing a pre -determined amount of one or more therapeutic agents of the present disclosure, as a powder or granules or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion or a water-in-oil liquid emulsion. Such compositions may be prepared by any of the methods of pharmacy but all methods include the step of bringing into association one or more agents as described above with the carrier which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the agents of the present disclosure with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation.

[1393] The above compositions may be administered in a manner compatible with the dosage formulation, and in such amount as is pharmaceutically-effective. The dose administered to a patient, in the context of the present disclosure, should be sufficient to effect a beneficial response in a patient over an appropriate period of time. The quantity of agent(s) to be administered may depend on the subject to be treated inclusive of the age, sex, weight and general health condition thereof, factors that will depend on the judgement of the practitioner.

[1394] It is envisaged that the various agents, anti-cancer agents or cancer treatments described herein can be formulated as discrete doses, such as in the form of a kit. Such a kit may further comprise a package insert comprising printed instructions for simultaneous, concurrent, sequential, successive, alternate or separate use of the agents in the treatment, amelioration and / or prevention of cancer, as described herein, in a patient in need thereof. Accordingly, the aforementioned kits are suitably for use in a method of treating, ameliorating and / or preventing cancer, inclusive of one or more symptoms, consequences, sequelae or complications thereof, as described herein.

[1395] Alternatively, the various therapeutic agents described herein can be formulated together in a composition that optionally includes a pharmaceutically acceptable carrier, excipient or diluent.

[1396] Methods of treating cancer may be prophylactic, preventative or therapeutic and suitable for treatment of cancer in mammals, particularly humans. As used herein, “treating”, “treat” or “treatment” refers to a therapeutic intervention, course of action or protocol that at least ameliorates a symptom of cancer after the cancer and / or its symptoms have at least started to develop. As used herein, “preventing”, “prevent” or “prevention” refers to therapeutic intervention, course of action or protocol initiated prior to the onset of cancer and / or a symptom of cancer so as to prevent, inhibit or delay or development or progression of the cancer or the symptom.

[1397] Anti-cancer treatments

[1398] The skilled person will appreciate that cancer treatments for use in the methods described herein may include drug therapy, chemotherapy, antibody, nucleic acid and other biomolecular therapies, radiation therapy, surgery, nutritional therapy, relaxation or meditational therapy and other natural or holistic therapies, although without limitation thereto. Generally, drugs, biomolecules (e.g., antibodies, inhibitory nucleic acids such as siRNA) or chemotherapeutic agents are referred to herein as “anti-cancer therapeutic agents” or “anti-cancer agents”.

[1399] Suitably, the treatment is or comprises one or more of chemotherapy, radiation therapy, molecularly targeted therapy and immunotherapy. It is envisaged that the treatment described herein can be administered prior to and / or after surgical resection of the oropharyngeal cancer in the subject. In particular examples, the treatment is administered prior to surgical resection of the oropharyngeal cancer in the subject. In other examples, the treatment is administered after surgical resection of the oropharyngeal cancer in the subject. For some examples, the treatment is administered before and after surgical resection of the oropharyngeal cancer in the subject. To this end, the treatment in question may be considered to be an adjuvant treatment. “Adjuvant” broadly refers to treatment given after administration or application of an initial anti-cancer treatment, such as surgical resection in a subject. As generally used herein, the term “chemotherapy” or “chemotherapeutic agent” broadly refers to a treatment or agent with a cytostatic or cytotoxic agent (i.e., a compound) to reduce or eliminate the growth or proliferation of undesirable cells, such as cancer cells. Accordingly, the terms can refer to a cytotoxic or cytostatic agent used to treat a proliferative disorder, for example cancer. The cytotoxic effect of the agent can be, but is not required to be, the result of one or more of nucleic acid intercalation or binding, DNA or RNA alkylation, inhibition of RNA or DNA synthesis, the inhibition of another nucleic acid-related activity (e.g., protein synthesis), or any other cytotoxic effect.

[1400] Exemplary chemotherapeutic agents include, but are not limited to, alkylating agents (e.g., nitrogen mustards such as chlorambucil, cyclophosphamide, isofamide, mechlorethamine, melphalan, and uracil mustard; aziridines such as thiotepa; methanesulphonate esters such as busulfan; nitroso ureas such as carmustine, lomustine, and streptozocin; platinum complexes such as cisplatin and carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, satraplatin and lipoplatin; bioreductive alkylators such as mitomycin, procarbazine, dacarbazine and altretamine); DNA strand-breakage agents (e.g., bleomycin); topoisomerase II inhibitors (e.g., amsacrine, dactinomycin, daunorubicin, idarubicin, mitoxantrone, doxorubicin, etoposide, and teniposide); DNA minor groove binding agents (e.g., plicamydin); antimetabolites (e.g., folate antagonists such as methotrexate and trimetrexate; pyrimidine antagonists such as fluorouracil, fluorodeoxyuridine, CB3717, azacitidine, cytarabine, and floxuridine; purine antagonists such as mercaptopurine, 6-thioguanine, fludarabine, pentostatin; asparginase; and ribonucleotide reductase inhibitors such as hydroxyurea); tubulin interactive agents (e.g., vincristine, vinblastine, and paclitaxel (Taxol)); hormonal agents (e.g., estrogens; conjugated estrogens; ethinyl estradiol; diethylstilbesterol; chlortrianisen; idenestrol; progestins such as hydroxyproge sterone caproate, medroxyprogesterone, and megestrol; and androgens such as testosterone, testosterone propionate, fluoxymesterone, and methyltestosterone); adrenal corticosteroids (e.g., prednisone, dexamethasone, methylprednisolone, and prednisolone); leutinizing hormone releasing agents or gonadotropin-releasing hormone antagonists (e.g., leuprolide acetate and goserelin acetate); and antihormonal antigens (e.g., tamoxifen, antiandrogen agents such as flutamide; and antiadrenal agents such as mitotane and aminoglutethimide).

[1401] In various examples, the chemotherapeutic agent is a platinum-based chemotherapeutic agent. The terms “platinum-based chemotherapy” and “platinum-based chemotherapeutic agent” as used interchangeably herein refer to a molecule or a composition comprising a molecule containing a coordination complex comprising the chemical element platinum and is useful as a chemotherapy drug. Platinum-based chemotherapy generally acts by inhibiting DNA synthesis and possesses some alkylating activity. Examples of platinum-based chemotherapy drugs include cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, satraplatin and lipoplatin. The platinum-based chemotherapy drug may be administered as a monotherapy, or in combination with other anti-cancer agents (e.g., an EGFR inhibitor), or as prodrugs, or together with local therapies such as surgery and radiation, or as adjuvant or neoadjuvant chemotherapy, or as part of a multimodal approach to the treatment of neoplastic disease. In particular examples, the chemotherapeutic agent is cisplatin and / or a variant, derivative or precursor thereof.

[1402] The term “radiation therapy” or “radiotherapy” used herein refers to the medical use of ionizing radiation, generally as part of cancer treatment, to control or destroy malignant cells. It can also be used as part of adjuvant therapy to prevent tumour recurrence after surgery to remove a primary malignant tumour. Radiation therapy can be synergistic with chemotherapy in oropharyngeal cancer and can be used before, during, and after chemotherapy in susceptible cancers.

[1403] Radiation therapy may be delivered by a device placed outside the patient’s body (external radiation therapy) or a source placed inside the patient’s body (internal radiation therapy or brachytherapy), or intravenously or orally. It may also be delivered by a systemically delivered radioisotope. Radiation therapy can be planned and administered in conjunction with imaging based techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI) to accurately determine the dose and location of radiation to be administered. In various embodiments, radiation therapy includes total body radiation therapy, conventional external beam radiation therapy, stereotactic radiosurgery, stereotactic radiation therapy, three-dimensional conformal radiation therapy, intensity modulated radiation therapy (IMRT), image-guided radiation therapy, tomotherapy and / or brachytherapy. In some examples, the radiation therapy includes stereotactic radiation therapy or intensity modulated radiation therapy (IMRT).

[1404] In specific examples, the radiation therapy is or comprises hypofractionated radiation therapy. Hypofractionated radiation therapy refers to radiation therapy in which a radiation dose is administered in 2 or more fractions. In various examples, each fraction comprises 2 to 20 Gy. For example, a radiation dose of 50 Gy may be split up into 10 fractions, each comprising 5 Gy.

[1405] In other examples, the radiation therapy is or comprises hyperfractionated radiation therapy. Hyperfractionated radiation therapy typically involves the regular administration of small doses of ionising radiation over a period of time, for example 0.1 Gy per hour over a number of days.

[1406] In particular examples, the treatment is chemoradiotherapy (CRT), which refers to the combined administration of both chemotherapy and radiotherapy as an anticancer treatment to a subject. The chemotherapy and radiotherapy can be concurrent or sequential. The term “radiochemotherapy” may be used interchangeably herein with the term “chemoradiotherapy”. CRT may include any combination of type, form or modality of chemotherapy and radiotherapy as are known in the art, such as those described herein.

[1407] As used herein, “molecularly targeted therapy” or “molecularly targeted therapeutic agent” refers to a therapy that targets a particular class of proteins involved in cancer growth or signalling. In some examples, the anti-cancer agent described herein is or comprises an inhibitor of a tyrosine kinase. The term “tyrosine kinase” refers to enzymes which are capable of transferring a phosphate group from ATP to a tyrosine residue in a protein. Phosphorylation of proteins by tyrosine kinases is an important mechanism in signal transduction for regulation of enzyme activity and cellular events such as cell survival or proliferation.

[1408] In particular examples, the molecularly targeted therapy is or comprises an EGFR inhibitor. The term “epidermal growth factor receptor” or “EGFR” as used herein refers to a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. It refers to a tyrosine kinase which regulates signalling pathways and growth and survival of cells and which shows affinity for the EGF molecule. The ErbB family of receptors consists of four closely related subtypes: ErbBl (epidermal growth factor receptor; EGFR), ErbB2 (HER2 / neu), ErbB3 (HER3), and ErbB4 (HER4) and variants thereof (e.g., a deletion mutant EGFR as in Humphrey et al. (Proc. Natl. Acad. Sci. USA, 1990, 87:4207-4211). Binding of an EGF ligand activates the EGFR (e.g., resulting in activation of intracellular mitogenic signalling and autophosphorylation of EGFR). One of skill in the art will understand that other ligands, in addition to EGF, can bind to and activate the EGFR. Examples of such ligands include, but are not limited to, amphiregulin, epiregulin, TGF-a, betacellulin (BTC), and heparin- binding EGF (HB-EGF).

[1409] As used herein, the term “EGFR inhibitor” refers to compounds that bind to or otherwise interact directly with EGFR (or any of its sequence variants, deletion or insertion mutants as are known in the art) and prevent or reduce its signalling activity, and is alternatively referred to as an “EGFR antagonist”. Examples of such agents include antibodies and small molecules that bind to EGFR.

[1410] Exemplary EGFR inhibitors include the anti-EGFR antibodies: cetuximab (Erbitux®), panitumumab (Vectibix®), matuzumab, nimotuzumab; and small molecule EGFR inhibitors: Tarceva® (erlotinib), IRESSA (gefitinib), 87stekinumab, EKB-569 (pelitinib, irreversible EGFR TKI), pan-ErbB and other receptor tyrosine kinase inhibitors, lapatinib (EGFR and HER2 inhibitor), pelitinib (EGFR and HER2 inhibitor), vandetanib (ZD6474, ZACTIMA™, EGFR, VEGFR2 and RET TKI), PF00299804 (dacomitinib, irreversible pan-ErbB TKI), CI- 1033 (irreversible pan-erbB TKI), afatinib (BIBW2992, irreversible pan-ErbB TKI), AV-412 (dual EGFR and ErbB2 inhibitor), EXEL-7647 (EGFR, ErbB2, GEVGR and EphB4 inhibitor), CO- 1686 (irreversible mutant- selective EGFR TKI), AZD9291 (irreversible mutant-selective EGFR TKI), and HKI-272 (neratinib, irreversible EGFR / ErbB2 inhibitor). In some examples, the EGFR inhibitor is or comprises cetuximab.

[1411] In particular examples, the treatment is or comprises CRT and optionally a molecularly targeted therapy, such as an EGFR inhibitor. More particularly, the treatment can be or comprise CRT and optionally an anti-EGFR antibody, such as cetuximab. In other examples, the treatment is or comprises radiotherapy and optionally a molecularly targeted therapy, such as an EGFR inhibitor. More particularly, the treatment can be or comprise radiotherapy and optionally an anti- EGFR antibody, such as cetuximab. For some examples, the treatment is or comprises a chemotherapeutic agent, such as a platinum-based chemotherapeutic agent (e.g., cisplatin), and optionally a molecularly targeted therapy, such as an EGFR inhibitor. More particularly, the treatment can be or comprise a chemotherapeutic agent, such as a platinum-based chemotherapeutic agent (e.g., cisplatin), and optionally an anti-EGFR antibody, such as cetuximab.

[1412] Insofar as they relate to cancer, immunotherapy or immunotherapeutic agents use or modify the immune mechanisms of a subject so as to promote or facilitate treatment of a cancer. In this regard, immunotherapy or immunotherapeutic agents used to treat cancer include cell-based therapies, antibody therapies (e.g., anti-PDl or anti-PDLl antibodies) and cytokine therapies. These therapies all exploit the phenomenon that cancer cells often have subtly different molecules termed cancer antigens on their surface that can be detected by the immune system of the cancer subject. Accordingly, immunotherapy is used to provoke the immune system of a cancer patient into attacking the cancer’s cells by using these cancer antigens as targets.

[1413] Non-limiting examples of immunotherapy or immunotherapeutic agents include adalimumab, alemtuzumab, basiliximab, belimumab, bevacizumab, BMS-936559, brentuximab, certolizumab, cetuximab, daclizumab, eculizumab, ibritumomab, infliximab, ipilimumab, lambrolizumab, mepolizumab, MPDL3280A muromonab, natalizumab, nivolumab, ofatumumab, omalizumab, pembrolizumab, pexelizumab, pidilizumab, rituximab, tocilizumab, tositumomab, trastuzumab, 88stekinumab, abatacept, alefacept and denileukin diftitox. In particular preferred embodiments, the immunotherapeutic agent is an immune checkpoint inhibitor, such as an anti- PDl antibody (e.g., pidilizumab, nivolumab, lambrolizumab, pembrolizumab), an anti-PDLl antibody (e.g., BMS-936559, MPDL3280A) and / or an anti-CTLA4 antibody (e.g., ipilimumab).

[1414] Protein biomarkers As described herein, the inventors have found that the expression levels of particular protein biomarkers, inclusive of phosphoprotein and phosphosite biomarkers, in biopsy samples from subjects with oropharyngeal cancer can correlate with disease prognosis, cancer aggressiveness and treatment response in these patients.

[1415] By “protein” is meant an amino acid polymer. The amino acids may be natural or nonnatural amino acids, D- or L- amino acids as are well understood in the art. As would be appreciated by the skilled person, the term “protein” also includes within its scope phosphorylated forms of a protein (z.e., a phosphoprotein) and / or glycosylated forms of a protein (z.e. a glycoprotein). A “peptide” is a protein having no more than fifty (50) amino acids. A “polypeptide” is a protein having more than fifty (50) amino acids.

[1416] The terms “phosphorylated form”, “phosphoprotein”, “phosphopeptide” and “phosphosite” as used herein, refer to the phosphorylated form of a protein or peptide, where a phosphate group (PCb)3-is added to the protein or peptide sequence at one or more of the amino acid groups, such as serine, tyrosine or threonine, giving an increase in mass corresponding to HPO3. In particular examples, the phosphoprotein, phosphopeptide or phosphosite may have one or a plurality (e.g., 1, 2, 3, 4, 5 etc) of phosphorylated amino acid groups therein. In particular examples, a phosphosite refers to a particular phosphorylated form of a phosphoprotein or phosphopeptide, in which a particular site thereon is modified by phosphorylation. More particularly, it is envisaged that an expression level of a phosphorylated form of a protein biomarker, such as those provided herein, can be determined at least in part by determining a level of a phosphopeptide or phosphosite derived therefrom. Unless specified otherwise, any reference to a biomarker herein includes modified forms thereof and more particularly phosphorylated forms thereof, as are provided herein.

[1417] Also provided herein are protein “variants” such as naturally occurring (e.g. allelic variants) and orthologs of the protein biomarkers provided herein. Suitably, protein variants share at least 70% or 75%, particularly at least 80% or 85% or more particularly at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity with an amino acid sequence of a protein biomarker disclosed herein (e.g., SEQ ID NOs:l to 1447) or known in the art.

[1418] Also provided are protein fragments, inclusive of peptide fragments that comprise less than 100% of an entire amino acid sequence. In particular examples, a protein fragment may comprise, for example, at least about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1050, 1100, 1150, 1200, 1250, 1300, 1350, 1400, 1450, 1500, 1550, 1600, 1650, 1700 and 1720 contiguous amino acids of said protein.

[1419] The term “biomarker” as used herein refers to a peptide, polypeptide or protein (including for example glycosylated proteins, and / or protein fragments) whose levels are associated with, for example, tumour responsiveness to treatment, tumour aggressiveness and patient outcomes, such as tumour recurrence, progression and metastasis. It will be appreciated that the term “biomarker” is intended to encompass all forms (e.g., phosphorylated and glycosylated forms), fragments and variants of a protein biomarker, as are known in the art, such as those provided in SEQ ID NOs: 1-1447 below.

[1420] Proteins in the prognostic signature

[1421] As noted above, the present inventors have identified a 20 protein signature that can be utilised clinically to correlate with disease prognosis, cancer aggressiveness and treatment response in oropharyngeal cancer patients. The amino acid sequences provided below are the ‘canonical’ or representative sequences for each of the respective proteins of the 20 protein signature. It is contemplated, however, that these proteins can encompass variants of the provided sequence (e.g., splice variants, SNPs, polymorphisms, genetically encoded variants, such as extensions, insertions and deletions), such as those known in the art.

[1422] ACP2 (Lysosomal Acid Phosphatase 2) is an enzyme with an acidic pH optimum that is expressed in the lysosomal compartment. The sequence of ACP2 is publicly available (e.g., UniProt Accession No. Pill 17). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 1. Thus, the ACP2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:1 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ACP2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ACP2 may be particularly amenable to mass spectrometry by, for example, multiple reaction monitoring (MRM) analysis.

[1423] ACP2 (SEQ ID NO: 1)

[1424] AGA (Aspartylglucosaminidase, EC 3.5.1.26) acts as a key enzyme in the catabolism of N-linked oligosaccharides of glycoproteins. The sequence of AGA is publicly available (e.g., UniProt Accession No. P20933). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 2. Thus, the AGA amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:2 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the AGA amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, AGA may be particularly amenable to MRM analysis.

[1425] AGA (SEQ ID NO: 2) BORCS6 (BORC subunit 6, C17ORF59, Lysosome-dispersing protein, Lyspersin) is a subunit of the BLOCl-related complex, or BORC, which has a role in regulating lysosome positioning. The sequence of BORCS6 is publicly available (e.g., UniProt Accession No. Q96GS4). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 3. Thus, the B0RCS6 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:3 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the B ORCS 6 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, BORCS6 may be particularly amenable to MRM analysis.

[1426] BORCS6 (SEQ ID NO: 3) COL8A1 (Collagen alpha- 1 (VIII) chain) is a macromolecular component of the subendothelium and may have a role in the maintenance of vessel wall integrity and structure. The sequence of COL8A1 is publicly available (e.g., UniProt Accession No. P27658). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 4. Thus, the COL8A1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:4 or a fragment or derivative thereof. Given its length, COL8A1 may be particularly amenable to MRM analysis.

[1427] COL8A1 (SEQ ID NO: 4)

[1428] DOK3 (Docking Protein 3; DOK-like Protein; DOKL) is an enzymatically inert adaptor or scaffolding protein that provides a docking platform for the assembly of multi-molecular signalling complexes. The sequence of DOK3 is publicly available (e.g., UniProt Accession No. Q7L591).

[1429] An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 5. Thus, the DOK3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 5 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the DOK3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, DOK3 may be particularly amenable to MRM analysis.

[1430] DOK3 (SEQ ID NO: 5)

[1431] ETHE1 (Hepatoma subtracted clone one, HSCO) a mitochondrial sulphur dioxygenase involved in the catabolism of sulphide. The sequence of ETHE1 is publicly available (e.g., UniProt Accession No. 095571). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 6. Thus, the ETHE1 amino acid sequence may be a protein which is at least 70%, 75%, 80%,

[1432] 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 6 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ETHE1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ETHE1 may be particularly amenable to MRM analysis.

[1433] ETHE1 (SEQ ID NO: 6) FNBP1 (Formin-binding protein 1) is responsible for coordinating membrane tabulation with reorganization of the actin cytoskeleton during the late stage of clathrin -mediated endocytosis. The sequence of FNBP1 is publicly available (e.g., UniProt Accession No. Q96RU3). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 7. Thus, the FNBP1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:7 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the FNBP1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, FNBP1 may be particularly amenable to MRM analysis.

[1434] FNBP1 (SEQ ID NO: 7) GOLGA3 (Golgin subfamily A member 3) appears to be involved in maintaining Golgi structure. The sequence of GOLGA3 is publicly available (e.g., UniProt Accession No. Q08378). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 8. Thus, the GOLGA3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 8 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the GOLGA3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, GOLGA3 may be particularly amenable to MRM analysis.

[1435] GOLGA3 (SEQ ID NO: 8) GSTO1 (Glutathione S-transferase omega- 1) is an enzyme that participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. The sequence of GSTO1 is publicly available (e.g., UniProt Accession No. P78417). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 9. Thus, the GSTO1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 9 or a fragment or derivative thereof. Given its length, GSTO1 may be particularly amenable to MRM analysis.

[1436] GSTO1 (SEQ ID NO: 9)

[1437] HAPLN3 (Hyaluronan And Proteoglycan Link Protein 3) may function in hyaluronic acid binding and cell adhesion. The sequence of HAPLN3 is publicly available (e.g., UniProt Accession No. Q96S86). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 10. Thus, the HAPLN3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 10 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the HAPLN3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, HAPLN3 may be particularly amenable to MRM analysis.

[1438] HAPLN3 (SEQ ID NO: 10)

[1439] HLA-DPA1 (HLA class II histocompatibility antigen, DP alpha 1 chain) is an MHC Class II protein that binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.

[1440] The sequence of HLA-DPA1 is publicly available (e.g., UniProt Accession No. P20036). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 11. Thus, the HLA-DPA1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 11 or a fragment or derivative thereof. Given its length, HLA-DPA1 may be particularly amenable to MRM analysis.

[1441] HLA-DPA1 (SEQ ID NO: 11) HLA-DRB4 (Major Histocompatibility Complex, Class II, DR Beta 4) plays a central role in the immune system by presenting peptides derived from extracellular proteins. The sequence of HLA-DRB4 is publicly available (e.g., UniProt Accession No. P13762). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 12. Thus, the HLA-DRB4 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 12 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the HLA-DRB4 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, HLA-DRB4 may be particularly amenable to MRM analysis.

[1442] HLA-DRB4 (SEQ ID NO: 12)

[1443] IGHM (Immunoglobulin heavy constant mu) forms the C region of the mu heavy chain of an immunoglobulin, which defines the IgM isotype. The sequence of IGHM is publicly available (e.g., UniProt Accession No. P01871). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 13. Thus, the IGHM amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 13 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the IGHM amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, IGHM may be particularly amenable to MRM analysis.

[1444] IGHM (SEQ ID NO: 13)

[1445] ITIH2 (Inter-alpha-trypsin inhibitor heavy chain H2) may act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein. The sequence of ITIH2 is publicly available (e.g., UniProt Accession No. P19823). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 14. Thus, the ITIH2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 14 or a fragment or derivative thereof.

[1446] ITIH2 (SEQ ID NO: 14)

[1447] IVL (Involucrin) is a keratinocyte protein that appears first in the cytoplasm but ultimately becomes cross-linked to membrane proteins by transglutaminase. The sequence of IVL is publicly available (e.g., UniProt Accession No. P07476). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 15. Thus, the IVL amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 15 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the IVL amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, IVL may be particularly amenable to MRM analysis.

[1448] IVL (SEQ ID NO: 15)

[1449]

[1450] MGST2 (Microsomal glutathione S-transferase 2) is a product of a gene superfamily that catalyze the conjugation of glutathione with a variety of xenobiotics and their reactive metabolites. The sequence of MGST2 is publicly available (e.g., UniProt Accession No. Q99735). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 16. Thus, the MGST2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 16 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the MGST2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, MGST2 may be particularly amenable to MRM analysis.

[1451] MGST2 (SEQ ID NO: 16)

[1452] PSMG1 (PAC1, Proteasome assembly chaperone 1) is involved in the maturation of mammalian 20S proteasomes. The sequence of PSMG1 is publicly available (e.g., UniProt Accession No. 095456). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 17. Thus, the PSMG1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 17 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the PSMG1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, PSMG1 may be particularly amenable to MRM analysis.

[1453] PSMG1 (SEQ ID NO: 17)

[1454] STAG1 (Cohesin subunit SA-1; SCC3 homolog 1; Stromal antigen 1) is a subunit of thecohesin complex, which has a crucial role in the control of chromosome segregation during cell division. The sequence of STAG1 is publicly available (e.g., UniProt Accession No. Q8WVM7). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 18. Thus, the STAG1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 18 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the STAG1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, STAG1 may be particularly amenable to MRM analysis.

[1455] STAG1 (SEQ ID NO: 18)

[1456] TAP2 (Antigen peptide transporter 2; ABCB3, PSF2, RING11, Yl) is a subunit of the

[1457] ATP-binding cassette transporter, TAP, which translocates peptides from the cytosol to awaiting

[1458] MHC class I molecules in the endoplasmic reticulum. The sequence of TAP2 is publicly available

[1459] (e.g., UniProt Accession No. Q03519). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 19. Thus, the TAP2 amino acid sequence may be a protein which is at least 70%,

[1460] 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 19 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the TAP2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, TAP2 may be particularly amenable to MRM analysis.

[1461] TAP2 (SEQ ID NO: 19)

[1462] UGDH (UDP-Glucose Dehydrogenase, UDPGDH) converts UDP-glucose (UDP-glc) to UDP-glucuronate / UDP-glucuronic acid (UDP-GlcA) through the concomitant reduction of NAD+ into NADH. The sequence of UGDH is publicly available (e.g., UniProt Accession No. 060701). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 20. Thus, the UGDH amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:20 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the UGDH amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, UGDH may be particularly amenable to MRM analysis. UGDH (SEQ ID NO: 20)

[1463] Proteins and peptides in the prognostic signatures

[1464] As noted above, the present inventors have identified a 26 peptide -based signature that can be utilised clinically to correlate with disease prognosis, cancer aggressiveness and treatment response in oropharyngeal cancer patients. The amino acid sequences provided below are the ‘canonical’ or representative sequences for each of the respective proteins of the 26 peptide -based signature. It is contemplated, however, that these proteins can encompass variants of the provided sequence (e.g., splice variants, SNPs, polymorphisms, genetically encoded variants, such as extensions, insertions and deletions), such as those known in the art. The peptides highlighted in yellow represent those preferred peptides of each corresponding protein that may be detected by, for example, mass spectrometry and more particularly MRM analysis, as outlined in more detail below.

[1465] AGRN (Agrin) is a component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The sequence of AGRN is publicly available (e.g., UniProt Accession No. 000468). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 21. Thus, the AGRN amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 21 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the AGRN amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, AGRN may be particularly amenable to MRM analysis. AGRN (SEQ ID NO: 21)

[1466] ALDOA (Fructose-bisphosphate aldolase A) is a glycolytic enzyme that catalyzes the reversible conversion of fructose- 1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The sequence of ALDOA is publicly available (e.g., UniProt Accession No. P04075). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 22. Thus, the ALDOA amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:22 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ALDOA amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ALDOA may be particularly amenable to MRM analysis.

[1467] ALDOA (SEQ ID NO: 22)

[1468] ARL6IP5 (PRA1 family protein 3; PRAF3) regulates intracellular concentrations of taurine and glutamate. The sequence of ARL6IP5 is publicly available (e.g., UniProt Accession No. 075915). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 23. Thus, the ARL6IP5 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 23 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ARL6IP5 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. ARL6IP5 (SEQ ID NO: 23)

[1469] ATP2A2 (Sarcoplasmic / endoplasmic reticulum calcium ATPase 2) is a magnesiumdependent enzyme that catalyses the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. The sequence of ATP2A2 is publicly available (e.g., UniProt Accession No. 075110). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 24. Thus, the ATP2A2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 24 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ATP2A2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ATP2A2 may be particularly amenable to MRM analysis.

[1470] ATP2A2 (SEQ ID NO: 24)

[1471]

[1472] CDS2 (Phosphatidate cytidylyltransferase 2, CDP-diacylglycerol synthase 2) is an enzyme which regulates the amount of phosphatidylinositol available for signalling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. The sequence of CDS2 is publicly available (e.g., UniProt Accession No. 095674). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 25. Thus, the CDS2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 25 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the CDS2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, CDS2 may be particularly amenable to MRM analysis.

[1473] CDS2 (SEQ ID NO: 25) CNDP2 (Cytosolic non-specific dipeptidase) is an enzyme that catalyses the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides. The sequence of CNDP2 is publicly available (e.g., UniProt Accession No. Q96KP4). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 26. Thus, the CNDP2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 26 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the CNDP2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, CNDP2 may be particularly amenable to MRM analysis.

[1474] CNDP2 (SEQ ID NO: 26) CTSZ (Cathepsin Z) is a member of the papam family of cysteine proteinases. The sequence of CTSZ is publicly available (e.g., UniProt Accession No. Q9UBR2). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 27. Thus, the CTSZ amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:27 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the CTSZ amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, CTSZ may be particularly amenable to MRM analysis.

[1475] CTSZ (SEQ ID NO: 27)

[1476] DECR1 (2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial) is an auxiliary enzyme of beta oxidation. The sequence of DECR1 is publicly available (e.g., UniProt

[1477] Accession No. Q16698). An exemplary canonical amino acid sequence is set forth in SEQ ID NO:

[1478] 28. Thus, the DECR1 amino acid sequence may be a protein which is at least 70%, 75%, 80%,

[1479] 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:28 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the DECR1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein.

[1480] Given its length, DECR1 may be particularly amenable to MRM analysis.

[1481] DECR1 (SEQ ID NO: 28)

[1482] ERP29 (Endoplasmic reticulum resident protein 29) plays an important role in the processing of secretory proteins within the endoplasmic reticulum. The sequence of ERP29 is publicly available (e.g., UniProt Accession No. P30040). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 29. Thus, the ERP29 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:29 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ERP29 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ERP29 may be particularly amenable to MRM analysis.

[1483] ERP29 (SEQ ID NO: 29)

[1484] GAPVD1 (GTPase-activating protein and VPS9 domain-containing protein 1) has both GTPase activating and inactivating domains, which acts as a guanine nucleotide exchange factor (GEF) for the RAB5a GTPase. The sequence of GAPVD1 is publicly available (e.g., UniProt Accession No. Q14C86). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 30. Thus, the GAPVD1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 30 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the GAPVD1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, GAPVD1 may be particularly amenable to MRM analysis.

[1485] GAPVD1 (SEQ ID NO: 30)

[1486] GARS1 (Glycine-tRNA ligase) is a glycyl-tRNA synthetase, an enzyme that is responsible for covalently attaching glycine to its cognate tRNA, which is essential for protein translation. The sequence of GARS1 is publicly available (e.g., UniProt Accession No. P41250). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 31. Thus, the GARS1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 31 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the GARS 1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, GARS1 may be particularly amenable to MRM analysis.

[1487] GARS1 (SEQ ID NO: 31)

[1488] HLA-A (HLA class I histocompatibility antigen, A alpha chain) is an antigen-presenting major histocompatibility complex class I (MHCI) molecule. The sequence of HLA-A is publicly available (e.g., UniProt Accession No. P04439). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 32. Thus, the HLA-A amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 32 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the HLA-A amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, HLA-A may be particularly amenable to MRM analysis.

[1489] HLA-A (SEQ ID NO: 32)

[1490] KRT17 (Keratin, type I cytoskeletal 17) is a cytokeratin normally expressed in the basal cells of complex epithelia but not in stratified or simple epithelia. The sequence of KRT17 is publicly available (e.g., UniProt Accession No. Q04695). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 33. Thus, the KRT17 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 33 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the KRT17 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, KRT17 may be particularly amenable to MRM analysis.

[1491] KRT17 (SEQ ID NO: 33)

[1492] LAP3 (Cytosol aminopeptidase, Leucine aminopeptidase 3) is a cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The sequence of LAP3 is publicly available (e.g., UniProt Accession No. P28838). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 34. Thus, the LAP3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 34 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the LAP3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, LAP3 may be particularly amenable to MRM analysis.

[1493] LAP3 (SEQ ID NO: 34)

[1494] LMNB1 (Lamin-Bl) is a component of the interphase nuclear lamina and is required to maintain nuclear shape and mechanical integrity. The sequence of LMNB1 is publicly available (e.g., UniProt Accession No. P20700). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 35. Thus, the LMNB1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 35 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the LMNB1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, LMNB 1 may be particularly amenable to MRM analysis. LMNB1 (SEQ ID NO: 35)

[1495]

[1496] MMP2 (matrix metalloproteinase 2, 72 kDa type IV collagenase) is a metalloproteinase that specifically cleaves type IV collagen, the major structural component of basement membranes. The sequence of MMP2 is publicly available (e.g., UniProt Accession No. P08253). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 36. Thus, the MMP2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 36 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the MMP2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, MMP2 may be particularly amenable to MRM analysis.

[1497] MMP2 (SEQ ID NO: 36)

[1498] MVP (Major vault protein) is the major component of the vault complex that is a multisubunit ribonucleoprotein structure, which may be involved in nucleo-cytoplasmic transport. The sequence of MVP is publicly available (e.g., UniProt Accession No. Q14764). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 37. Thus, the MVP amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:37 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the MVP amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, MVP may be particularly amenable to MRM analysis.

[1499] MVP (SEQ ID NO: 37)

[1500]

[1501] NOP56 (Nucleolar protein 56) is a component of the box C / D small nucleolar ribonucleoprotein complexes that direct 2-prime-O-methylation of pre-ribosomal RNA (rRNA) during its maturation. The sequence of NOP56 is publicly available (e.g., UniProt Accession No. 000567). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 38. Thus, the

[1502] NOP56 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 38 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the NOP56 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, NOP56 may be particularly amenable to MRM analysis.

[1503] NOP56 (SEQ ID NO: 38)

[1504] OPA3 (Optic atrophy 3 protein) may have a role in mitochondrial processes. The sequence of OPA3 is publicly available (e.g., UniProt Accession No. Q9H6K4). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 39. Thus, the OPA3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 39 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the OPA3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein.

[1505] OPA3 (SEQ ID NO: 39)

[1506] PSMB4 (Proteasome subunit beta type-4) is a non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. The sequence of PSMB4 is publicly available (e.g., UniProt Accession No. P28070). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 40. Thus, the PSMB4 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 40 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the PSMB4 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, PSMB4 may be particularly amenable to MRM analysis.

[1507] PSMB4 (SEQ ID NO: 40) S100A4 (HLA class I histocompatibility antigen, A alpha chain) is an antigen-presenting major histocompatibility complex class I (MHCI) molecule. The sequence of S100A4 is publicly available (e.g., UniProt Accession No. P26447). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 41. Thus, the S 100A4 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 41 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the S100A4 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, S100A4 may be particularly amenable to MRM analysis.

[1508] S100A4 (SEQ ID NO: 41)

[1509] SPRR3 (Small proline-rich protein 3) is a component of the cornified cell envelope, which provides the protective barrier function of stratified squamous epithelial cells. The sequence of SPRR3 is publicly available (e.g., UniProt Accession No. Q9UBC9). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 42. Thus, the SPRR3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 42 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the SPRR3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, SPRR3 may be particularly amenable to MRM analysis.

[1510] SPRR3 (SEQ ID NO: 42)

[1511] TCEA1 (Transcription elongation factor A protein 1) is necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The sequence of TCEA1 is publicly available (e.g., UniProt Accession No. P23193). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 43. Thus, the TCEA1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 43 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the TCEA1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, TCEA1 may be particularly amenable to MRM analysis.

[1512] TCEA1 (SEQ ID NO: 43)

[1513] WDR81 (WD repeat-containing protein 81) functions as a negative regulator of the PI3 kinase / PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. The sequence of WDR81 is publicly available (e.g., UniProt Accession No. Q562E7). An exemplary canonical amino acid sequence is set forth in SEQ ID NO: 44. Thus, the WDR81 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 44 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the WDR81 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, WDR81 may be particularly amenable to MRM analysis.

[1514] WDR81 (SEQ ID NO: 44)

[1515] Proteins, peptides and phosphopeptide in the prognostic signature

[1516] As noted above, the present inventors have identified a 26 phosphopeptide-based signature that can be utilised clinically to correlate with disease prognosis, cancer aggressiveness and treatment response in oropharyngeal cancer patients. The amino acid sequences provided below are the ‘canonical’ or representative sequences for each of the respective proteins of the 26 peptide- based signature. It is contemplated, however, that these proteins can encompass variants of the provided sequence (e.g., splice variants, SNPs, polymorphisms, genetically encoded variants, such as extensions, insertions and deletions), such as those known in the art. The peptides or phosphopeptides highlighted in yellow represent those preferred peptides or phosphopeptides of each corresponding protein that may be detected by, for example, mass spectrometry and more particularly MRM analysis, as outlined in more detail below.

[1517] ACTB (beta-actin) is essential for a number of cytoplasmic functions, such as regulation of cell shape and migration, as well as nuclear functions, such as regulation of gene expression, cell division, and proliferation. The sequence of ACTB is publicly available (e.g., UniProt Accession No. P60709). An exemplary amino acid sequence is set forth in SEQ ID NO: 627. Thus, the ACTB amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 627 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ACTB amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ACTB may be particularly amenable to MRM analysis.

[1518] ACTB (SEQ ID NO: 627) ATP5F1B (ATP synthase subunit beta, mitochondrial) is the beta subunit of the mitochondrial ATP synthase Fl complex. The sequence of ATP5F1B is publicly available (e.g., UniProt Accession No. P06576). An exemplary amino acid sequence is set forth in SEQ ID NO: 628. Thus, the ATP5F1B amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 628 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ATP5F1B amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ATP5F1B may be particularly amenable to MRM analysis. ATP5F1B (SEQ ID NO: 628)

[1519] ATP5F1D (ATP synthase subunit delta, mitochondrial) is the delta subunit of the mitochondrial ATP synthase Fl complex. The sequence of ATP5F1D is publicly available (e.g., UniProt Accession No. P30049). An exemplary amino acid sequence is set forth in SEQ ID NO: 629. Thus, the ATP5F1D amino acid sequence may be a protein which is at least 70%, 75%, 80%,

[1520] 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO:629 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ATP5F1D amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ATP5F1D may be particularly amenable to MRM analysis.

[1521] ATP5F1D (SEQ ID NO: 629)

[1522] CDKN2A (Cyclin-dependent kinase inhibitor 2A; pl6INK4a) regulates two critical cell cycle regulatory pathways, the p53 pathway and the RBI pathway. The sequence of CDKN2A is publicly available (e.g., UniProt Accession No. P42771). An exemplary amino acid sequence is set forth in SEQ ID NO: 630. Thus, the CDKN2A amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 630 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the CDKN2A amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, CDKN2A may be particularly amenable to MRM analysis.

[1523] CDKN2A (pl6INK4a) (SEQ ID NO: 630)

[1524] DARS (Aspartate-tRNA ligase, mitochondrial) is an enzyme that catalyses the aminoacylation of tRNA and production of tRNA-aspartyl. The sequence of DARS is publicly available (e.g., UniProt Accession No. Q6PI48). An exemplary amino acid sequence is set forth in SEQ ID NO: 631. Thus, the DARS amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 631 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the DARS amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, DARS may be particularly amenable to MRM analysis.

[1525] DARS (SEQ ID NO: 631)

[1526] EMILIN 1 may be responsible for anchoring smooth muscle cells to elastic fibres, and could be involved not only in the formation of the elastic fibre, but also in the processes that regulate vessel assembly. The sequence of EMILIN1 is publicly available (e.g., UniProt Accession No. Q9Y6C2). An exemplary amino acid sequence is set forth in SEQ ID NO: 632. Thus, the EMILIN1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 632 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the EMILIN1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, EMILIN1 may be particularly amenable to MRM analysis.

[1527] EMILIN1 (SEQ ID NO: 632)

[1528] ENO1 (Alpha-enolase) is a glycolytic enzyme the catalyses the conversion of 2- phosphogly cerate to phosphoenolpyruvate. The sequence of ENO1 is publicly available (e.g., UniProt Accession No. P06733). An exemplary amino acid sequence is set forth in SEQ ID NO: 633. Thus, the ENO1 amino acid sequence may be a protein which is at least 70%, 75%, 80%,

[1529] 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 633 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the ENO1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, ENO1 may be particularly amenable to MRM analysis.

[1530] ENO1 (SEQ ID NO: 633)

[1531]

[1532] EPPK1 (Epiplakin) is a cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to stress. The sequence of EPPK1 is publicly available (e.g., UniProt Accession No. P58107). An exemplary amino acid sequence is set forth in SEQ ID NO: 634. Thus, the EPPK1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 634 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the EPPK1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, EPPK1 may be particularly amenable to MRM analysis.

[1533] EPPK1 (SEQ ID NO: 634)

[1534]

[1535] FN 1 (Fibronectin) binds cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. The sequence of FN1 is publicly available (e.g., UniProt Accession No. P02751). An exemplary amino acid sequence is set forth in SEQ ID NO: 635. Thus, the FN1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 635 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the FN 1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, FN1 may be particularly amenable to MRM analysis.

[1536] FN1 (SEQ ID NO: 635)

[1537]

[1538] GNAI3 (Guanine nucleotide-binding protein G(i) subunit alpha-3) belongs to a group of heterotrimeric guanine nucleotide-binding proteins (G proteins) that function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signalling cascades. The sequence of GNAI3 is publicly available (e.g., UniProt Accession No. P08754). An exemplary amino acid sequence is set forth in SEQ ID NO: 636. Thus, the GNAI3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 636 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the GNAI3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, GNAI3 may be particularly amenable to MRM analysis.

[1539] GNAI3 (SEQ ID NO: 636)

[1540] GNL1 (Guanine nucleotide-binding protein-like 1) may have regulatory role with the histocompatibility cluster. The sequence of GNL1 is publicly available (e.g., UniProt Accession No. P36915). An exemplary amino acid sequence is set forth in SEQ ID NO: 637. Thus, the GNL1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 637 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the GNL1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, GNL1 may be particularly amenable to MRM analysis.

[1541] GNL1 (SEQ ID NO: 637)

[1542] GSR (Glutathione reductase, mitochondrial) has a regulatory role in maintaining high levels of reduced glutathione in the cytosol. The sequence of GSR is publicly available (e.g., UniProt Accession No. P00390). An exemplary amino acid sequence is set forth in SEQ ID NO: 638. Thus, the GSR amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%,

[1543] 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 638 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the GSR amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, GSR may be particularly amenable to MRM analysis.

[1544] GSR (SEQ ID NO: 638)

[1545] IGKV1-6 (Immunoglobulin kappa variable 1-6) is the V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition. The sequence of IGKV1- 6 is publicly available (e.g., UniProt Accession No. A0A0C4DH72). An exemplary amino acid sequence is set forth in SEQ ID NO: 639. Thus, the IGKV1-6 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 639 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the IGKV1-6 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, IGKV1-6 may be particularly amenable to MRM analysis.

[1546] IGKV1-6 (SEQ ID NO: 639) KRT6C (Keratin, type II cytoskeletal 6C) is an isoform of human type II keratin-6. The sequence of KRT6C is publicly available (e.g., UniProt Accession No. P48668). An exemplary amino acid sequence is set forth in SEQ ID NO: 640. Thus, the KRT6C amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 640 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the KRT6C amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, KRT6C may be particularly amenable to MRM analysis.

[1547] KRT6C (SEQ ID NO: 640)

[1548] MUC5B (Mucin-5B) may have regulatory role with the histocompatibility cluster. The sequence of MUC5B is publicly available (e.g., UniProt Accession No. Q9HC84). An exemplary amino acid sequence is set forth in SEQ ID NO: 641. Thus, the MUC5B amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 641 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the MUC5B amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, MUC5B may be particularly amenable to MRM analysis.

[1549] MUC5B (SEQ ID NO: 641)

[1550] MYH11 (Myosin-11) is involved in muscle contraction. The sequence of MYH11 is publicly available (e.g., UniProt Accession No. P35749). An exemplary amino acid sequence is set forth in SEQ ID NO: 642. Thus, the MYH11 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 642 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the MYH11 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, MYH11 may be particularly amenable to MRM analysis.

[1551] MYH11 (SEQ ID NO: 642)

[1552]

[1553] 0XCT1 (Succinyl-CoA:3-ketoacid coenzyme A transferase 1) is an enzyme that catalyses the first, rate -limiting step of ketone body utilization in extrahepatic tissues. The sequence of 0XCT1 is publicly available (e.g., UniProt Accession No. P55809). An exemplary amino acid sequence is set forth in SEQ ID NO: 643. Thus, the OXCT1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 643 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the OXCT1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, 0XCT1 may be particularly amenable to MRM analysis.

[1554] OXCT1 (SEQ ID NO: 643) PKP2 (Plakophilin-2) regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta- integrins. The sequence of PKP2 is publicly available (e.g., UniProt Accession No. Q99959). An exemplary amino acid sequence is set forth in SEQ ID NO: 644. Thus, the PKP2 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 644 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the PKP2 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, PKP2 may be particularly amenable to MRM analysis.

[1555] PKP2 (SEQ ID NO: 644)

[1556]

[1557] POSTN (Periostin) induces cell attachment and spreading and plays a role in cell adhesion. The sequence of POSTN is publicly available (e.g., UniProt Accession No. Q15063). An exemplary amino acid sequence is set forth in SEQ ID NO: 645. Thus, the POSTN amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 645 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the POSTN amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, POSTN may be particularly amenable to MRM analysis.

[1558] POSTN (SEQ ID NO: 645)

[1559] PRKDC (DNA-dependent protein kinase catalytic subunit) is a nuclear DNA-dependent serine / threonine protein kinase (DNA-PK), which is involved in DNA nonhomologous endjoining (NHEJ) during DNA double-strand break (DSB) repair and for V(D)J recombination during immune development. The sequence of PRKDC is publicly available (e.g., UniProt Accession No. P78527). An exemplary amino acid sequence is set forth in SEQ ID NO: 646. Thus, the PRKDC amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 646 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the PRKDC amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, PRKDC may be particularly amenable to MRM analysis.

[1560] PRKDC (SEQ ID NO: 646)

[1561]

[1562] PTBPl(Polypyrimidine tract-binding protein 1) plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. The sequence of PTBP1 is publicly available (e.g., UniProt Accession No. P26599). An exemplary amino acid sequence is set forth in SEQ ID NO: 647. Thus, the PTBP1 amino acid sequence may be a protein which is at least 70%, 75%, 80%,

[1563] 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 647 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the PTBP1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, PTBP1 may be particularly amenable to MRM analysis.

[1564] PTBP1 (SEQ ID NO: 647)

[1565] PTBP3 (polypyrimidine tract-binding protein 3) is an RNA-binding protein that mediates pre-mRNA alternative splicing regulation and plays a role in the regulation of cell proliferation, differentiation and migration. The sequence of PTBP3 is publicly available (e.g., UniProt Accession No. 095758). An exemplary amino acid sequence is set forth in SEQ ID NO: 648. Thus, the PTBP3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 648 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the PTBP3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, PTBP3 may be particularly amenable to MRM analysis.

[1566] PTBP3 (SEQ ID NO: 648)

[1567] RPS4X (Small ribosomal subunit protein eS4, X isoform) is a component of the small ribosomal subunit. The sequence of RPS4X is publicly available (e.g., UniProt Accession No. P62701). An exemplary amino acid sequence is set forth in SEQ ID NO: 649. Thus, the RPS4X amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 649 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the RPS4X amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, RPS4X may be particularly amenable to MRM analysis.

[1568] RPS4X (SEQ ID NO: 649)

[1569] SIK3 (Serine / threonine-protein kinase SIK3) is a positive regulator of mTOR signalling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. The sequence of SIK3 is publicly available (e.g., UniProt Accession No. Q9Y2K2). An exemplary amino acid sequence is set forth in SEQ ID NO: 650. Thus, the SIK3 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 650 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the SIK3 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, SIK3 may be particularly amenable to MRM analysis.

[1570] SIK3 (SEQ ID NO: 650)

[1571] STAU 1 (Double- stranded RNA-binding protein Staufen homolog 1) binds double- stranded RNA and tubulin and may play a role in the specific positioning of mRNAs at given sites in a cell by cross-linking cytoskeletal and RNA components, and in stimulating their translation at the site.

[1572] The sequence of STAU1 is publicly available (e.g., UniProt Accession No. 095793). An exemplary amino acid sequence is set forth in SEQ ID NO: 651. Thus, the STAU1 amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 651 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the STAU 1 amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, STAU1 may be particularly amenable to MRM analysis.

[1573] STAU1 (SEQ ID NO: 651)

[1574] TNC (tenascin C) is an extracellular matrix protein with a spatially and temporally restricted tissue distribution. The sequence of TNC is publicly available (e.g., UniProt Accession No. P24821). An exemplary amino acid sequence is set forth in SEQ ID NO: 652. Thus, the TNC amino acid sequence may be a protein which is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 100% identical to SEQ ID NO: 652 or a fragment or derivative thereof. Also provided below are peptide sequences contained within the TNC amino acid sequence that may be suitable for analysis by mass spectrometry, as described herein. Given its length, TNC may be particularly amenable to MRM analysis.

[1575] TNC (SEQ ID NO: 652)

[1576]

[1577] Suitably, the expression level of two or more of the protein biomarkers (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 protein biomarkers) provided herein, inclusive of peptide biomarkers and phosphopeptide biomarkers thereof (e.g., any of SEQ ID NOs: 1 to 1447), are determined for the methods described herein. This may include two or more protein biomarkers, inclusive of peptide biomarkers and phosphopeptide biomarkers, derived from two or more of the particular signatures described herein (i.e., two or more protein biomarkers from the 20 protein signature, the 26 peptide signature and the 26 phosphopeptide signature as provided in Table 4). Accordingly, the expression level of two or more of the protein biomarkers, inclusive of peptide biomarkers and phosphopeptide biomarkers thereof, (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 24, 25 or 26 protein biomarkers) selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1, WDR81, ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC are determined for the methods described herein.

[1578] In some examples, the methods described herein include the step of determining the expression level of three or more protein biomarkers described herein. In other examples, the methods described herein include the step of determining the expression level of four or more protein biomarkers described herein. In certain examples, the methods described herein include the step of determining the expression level of five or more protein biomarkers described herein. In some examples, the methods described herein include the step of determining the expression level of six or more protein biomarkers described herein. In various examples, the methods described herein include the step of determining the expression level of seven or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of eight or more protein biomarkers described herein. In some examples, the methods described herein include the step of determining the expression level of nine or more protein biomarkers described herein. In other examples, the methods described herein include the step of determining the expression level of ten or more protein biomarkers described herein. In certain examples, the methods described herein include the step of determining the expression level of eleven or more protein biomarkers described herein. In some examples, the methods described herein include the step of determining the expression level of twelve or more protein biomarkers described herein. In various examples, the methods described herein include the step of determining the expression level of thirteen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of fourteen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of fifteen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of sixteen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of seventeen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of eighteen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of nineteen or more protein biomarkers described herein. In particular examples, the methods described herein include the step of determining the expression level of twenty or more protein biomarkers described herein.

[1579] In other examples, the methods described herein include the step of determining the expression level of sixteen or more protein biomarkers described herein. Accordingly, in one example, the methods described herein include the step of determining an expression level of sixteen or more protein biomarkers, wherein the protein biomarkers comprise ACP2, AGA, BORCS6, DOK3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof. In this regard, the present methods may include determining a level of one or more peptide fragments independently having an amino acid sequence selected from the group consisting of SEQ ID NOs: 45 to 60, 63 to 93, 103 to 108, 112 to 131 and 155 to 223 (inclusive of fragments, variants or derivatives thereof) and / or one or more peptide fragments independently having an amino acid sequence derived from or contained within an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 3, 5 to 8, 10, 12 to 13 and 15 to 20 by mass spectrometry.

[1580] According to some examples, the methods described herein include the step of determining the expression level of twenty protein biomarkers described herein. Accordingly, in one example, the methods described herein include the step of determining an expression level of twenty or more protein biomarkers, wherein the protein biomarkers comprise ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof. In this regard, the present methods may include determining a level of one or more peptide fragments independently having an amino acid sequence selected from the group consisting of SEQ ID NOs: 45 to 223 (inclusive of fragments, variants or derivatives thereof) and / or one or more peptide fragments independently having an amino acid sequence derived from or contained within an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 20 by mass spectrometry.

[1581] In various examples, the methods described herein include the step of determining the expression level of at least about twenty protein biomarkers described herein. More particularly, the methods described herein include the step of determining the expression level of twenty-six protein biomarkers, or more particularly peptide biomarkers, described herein. Accordingly, in one example, the methods described herein include the step of determining an expression level of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof. To this end, the present methods may include determining a level of one or more peptide fragments independently having an amino acid sequence selected from the group consisting of SEQ ID NOs: 68 to 78, 185-191 and 224 to 626 (inclusive of fragments, variants or derivatives thereof) and / or one or more peptide fragments independently having an amino acid sequence derived from or contained within an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 18 and 21 to 44 by mass spectrometry. In particular examples, the present methods described herein include determining a level of each peptide fragment having an amino acid sequence set forth in SEQ ID NOs: 72, 189, 253, 284, 286, 302, 315, 331, 337, 347, 355, 367, 380, 399, 419, 447, 462, 500, 533, 552, 565, 573, 577, 596, 602 and 616 (inclusive of fragments, variants or derivatives thereof) by mass spectrometry.

[1582] In certain examples, the methods described herein include the step of determining the expression level of the phosphorylated form of eighteen protein biomarkers described herein. Accordingly, in one example, the methods described herein include the step of determining an expression level of a phosphorylated form of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof. To this end, the present methods may include determining a level of one or more peptide fragments independently having an amino acid sequence derived from or contained within an amino acid sequence selected from the group consisting of SEQ ID NOs: 627 to 652 by mass spectrometry. In particular examples, the present methods described herein include determining a level of a phosphopeptide and / or phosphosite derived from each of the one or more protein biomarkers. As such, the present methods may include determining a level of a phosphorylated form of one or more peptides (e.g., a phosphopeptide and / or phosphosite) having an amino acid sequence set forth in SEQ ID NOs: 653 to 1447 (inclusive of fragments, variants or derivatives thereof) by mass spectrometry. More particularly, the present methods may include determining a level of a phosphorylated form of one or more peptides (e.g., a phosphopeptide and / or phospho site) having an amino acid sequence set forth in SEQ ID NOs: 653, 672, 680, 684, 689, 704, 734, 770, 879, 880, 931, 971, 978, 981, 998, 1008, 1010, 1034, 1096, 1126, 1148, 1166, 1202, 1342, 1351, 1358, 1359, 1362, 1372, 1395, 1396 and 1397 (inclusive of fragments, variants or derivatives thereof) by mass spectrometry. Even more particularly, the present methods may include determining a level of a phosphorylated form of one or more peptides (e.g., a phosphopeptide and / or phosphosite) having an amino acid sequence set forth in SEQ ID NOs: 653, 680, 684, 689, 704, 734, 770, 880, 971, 978, 981, 998, 1008, 1010, 1034, 1096, 1126, 1148, 1166, 1202, 1342, 1351, 1358, 1362, 1372 and 1396 (inclusive of fragments, variants or derivatives thereof) by mass spectrometry. In particular examples, the present methods include determining a level of a phosphorylated form of each of the peptides set forth in SEQ ID NOs: 653, 672, 680, 684, 689, 704, 734, 770, 879, 880, 931, 971, 978, 981, 998, 1008, 1010, 1034, 1096, 1126, 1148, 1166, 1202, 1342, 1351, 1358, 1359, 1362, 1372, 1395, 1396 and 1397 (inclusive of fragments, variants or derivatives thereof) by mass spectrometry. In other examples, the present methods include determining a level of a phosphorylated form of each of the peptides set forth in SEQ ID NOs: 653, 680, 684, 689, 704, 734, 770, 880, 971, 978, 981, 998, 1008, 1010, 1034, 1096, 1126, 1148, 1166, 1202, 1342, 1351, 1358, 1362, 1372 and 1396 (inclusive of fragments, variants or derivatives thereof) by mass spectrometry. Exemplary phosphopeptides and phosphosites are provided above and in Table 3 herein.

[1583] Referring to some examples, the methods described herein include the step of determining an expression level of one or more protein biomarkers, inclusive of a phosphorylated form thereof, selected from, comprising or consisting of:

[1584] (i) ACP2, ACTB, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, ATP5F1B, ATP5F1D, BORCS6, CDKN2A, CDS2, CNDP2, COL8A1, CTSZ, DARS2, DECR1, DOK3, EMILIN1, ENO1, EPPK1, ERP29, ETHE1, FN1, FNBP1, GAPVD1, GARS1, GNAI3, GNL1, GOLGA3, GSR, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, IGKV1-6, ITIH2, IVL, KRT17, KRT6C, LAP3, LMNB1, MGST2, MMP2, MUC5B, MVP, MYH11, NOP56, OPA3, OXCT1, PKP2, POSTN, PRKDC, PSMB4, PSMG1, PTBP1, PTBP3, RPS4X, S100A4, SIK3, SPRR3, STAG1, STAU1, TAP2, TCEA1, TNC, UGDH and WDR81, or a fragment, variant or derivative thereof;

[1585] (ii) ACP2, AGA, AGRN, ALDOA, ARL6IP5, ATP2A2, BORCS6, CDS2, CNDP2, COL8A1, CTSZ, DECR1, DOK3, ERP29, ETHE1, FNBP1, GAPVD1, GARS1, GOLGA3, GSTO1, HAPLN3, HLA-A, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, KRT17, LAP3, LMNB1, MGST2, MMP2, MVP, NOP56, OPA3, PSMB4, PSMG1, S100A4, SPRR3, STAG1, TAP2, TCEA1, UGDH and WDR81, or a fragment, variant or derivative thereof;

[1586] (iii) ACP2, AGA, BORCS6, DOK3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof;

[1587] (iv) ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof;

[1588] (v) AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof; and / or

[1589] (vi) ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

[1590] In one example, the methods of the present disclosure include the step of determining an expression level of ACP2 and at least one further protein biomarker selected from the group consisting of AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof. In another example, the methods of the present disclosure include the step of determining an expression level of ACP2 and at least one further protein biomarker selected from the group consisting of AGA, BORCS6, DOK3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[1591] In one example, the methods of the present disclosure include the step of determining an expression level of AGA and at least one further protein biomarker selected from the group consisting of ACP2, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof. In another example, the methods of the present disclosure include the step of determining an expression level of AGA and at least one further protein biomarker selected from the group consisting of ACP2, BORCS6, DOK3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[1592] In one example, the methods of the present disclosure include the step of determining an expression level of BORCS6 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof. In another example, the methods of the present disclosure include the step of determining an expression level of BORCS6 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, D0K3, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[1593] In one example, the methods of the present disclosure include the step of determining an expression level of COL8A1 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, BORCS6, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof.

[1594] In one example, the methods of the present disclosure include the step of determining an expression level of DOK3 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof. In another example, the methods of the present disclosure include the step of determining an expression level of DOK3 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, BORCS6, ETHE1, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

[1595] In one example, the methods of the present disclosure include the step of determining an expression level of ETHE1 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof. In another example, the methods of the present disclosure include the step of determining an expression level of ETHE1 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, BORCS6, DOK3, FNBP1, GOLGA3, HAPLN3, HLA-DRB4, IGHM, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof. In one example, the methods of the present disclosure include the step of determining an expression level of FNBP1 and at least one further protein biomarker selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2, UGDH, and fragments, variants or derivatives thereof. In another example, the methods of the present disclosure include the step of determining an expression level of FNB...

Claims

CLAIMS:

1. A method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

2. A method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDO A, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

3. A method of determining a prognosis for a subject with an oropharyngeal cancer, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, to thereby determine the prognosis of the oropharyngeal cancer in the subject.

4. The method of Claim 3, wherein the step of determining the expression level of the phosphorylated form comprises determining a level of a phosphopeptide derived from the one or more protein biomarkers.

5. The method of any one of the preceding claims, wherein if the expression level of said one or more protein biomarkers is altered or modulated in the one or plurality of cancer cells, tissues or organs, the prognosis may be negative or positive.

6. The method of any one of the preceding claims, further including the steps of: calculating a risk score using the expression level of the one or more protein biomarkers; and comparing the risk score to a reference risk score, wherein, if (i) the risk score is equal to or higher than the reference risk score, the subject has a poor prognosis, and (ii) the risk score is lower than the reference risk score, the subject has a favourable prognosis.

7. The method of any one of the preceding claims, wherein the prognosis is used, at least in part, to determine whether the subject would benefit from a treatment of the oropharyngeal cancer.

8. The method of Claim 7, wherein the treatment is or comprises one or more of chemotherapy, radiation therapy, a molecularly targeted therapy and immunotherapy.

9. The method of any one of the preceding claims, wherein the prognosis is used, at least in part, to develop a treatment strategy for the subject.

10. The method of any one of the preceding claims, wherein the prognosis is defined as an estimated time of survival or an estimated risk of recurrence.

11. A method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA- DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level of responsiveness of the oropharyngeal cancer to the treatment.

12. A method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1,GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, 0PA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level of responsiveness of the oropharyngeal cancer to the treatment.

13. A method of predicting the responsiveness of an oropharyngeal cancer in a subject to a treatment, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, EN01, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, 0XCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, wherein the expression level of the one or more protein biomarkers indicates or correlates with a level of responsiveness of the oropharyngeal cancer to the treatment.

14. The method of Claim 13, wherein the step of determining the expression level of the phosphorylated form comprises determining an expression level of a phosphopeptide derived from the one or more protein biomarkers.

15. The method of any one of Claims 7 to 14, further including the step of administering the treatment for the oropharyngeal cancer to the subject.

16. A method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determined in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, C0L8A1, D0K3, ETHE1, FNBP1, G0LGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

17. A method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of one or more protein biomarkers has been determinedin one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDO A, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

18. A method of treating an oropharyngeal cancer in a subject, said method including the step of administering a therapeutically effective amount of a treatment for the oropharyngeal cancer to the subject in which an expression level of a phosphorylated form of one or more protein biomarkers has been determined in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, and wherein the expression level indicates or correlates with the oropharyngeal cancer being at least partly responsive to the treatment.

19. The method of Claim 18, wherein the step of determining the expression level of the phosphorylated form comprises determining an expression level of a phosphopeptide derived from the one or more protein biomarkers.

20. The method of any one of Claims 11 to 19, further including the steps of: calculating a risk score using the expression level of the one or more protein biomarkers; and comparing the risk score to a reference risk score, wherein, if (i) the risk score is equal to or higher than the reference risk score, the oropharyngeal cancer is not responsive to the treatment, and (ii) the risk score is lower than the reference risk score, the oropharyngeal cancer is at least partly responsive to the treatment.

21. A method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL,MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

22. A method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, 0PA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

23. A method of treating an oropharyngeal cancer in a subject, said method including the step of: determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1- 6, KRT6C, MUC5B, MYH11, 0XCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof, and based on the determination made, initiating, continuing, modifying or discontinuing a treatment of the oropharyngeal cancer.

24. The method of Claim 23, wherein the step of determining the expression level of the phosphorylated form comprises determining an expression level of a phosphopeptide derived from the one or more protein biomarkers.

25. The method of any one of Claims 11 to 24, wherein the treatment is or comprises one or more of chemotherapy, radiation therapy, a molecularly targeted therapy and immunotherapy.

26. The method of any one of Claims 21 to 25, further including the steps of: calculating a risk score using the expression level of the one or more protein biomarkers; and comparing the risk score to a reference risk score,wherein, if (i) the risk score is equal to or higher than the reference risk score, the subject is to be administered a first treatment, and (ii) the risk score is lower than the reference risk score, the subject is to be administered a second treatment.

27. The method of Claim 26, wherein: the first treatment does not include chemotherapy and / or radiation therapy; and / or the second treatment includes chemotherapy and / or radiation therapy.

28. The method of any one of the preceding claims, wherein the specificity and / or sensitivity of the method, as determined by an ROC AUC value, is at least about 0.65, at least about 0.70, at least about 0.75, at least about 0.80, at least about 0.85, at least about 0.90 or at least about 0.95.

29. A system for determining a prognosis for a subject with oropharyngeal carcinoma, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to determine the prognosis of the oropharyngeal cancer in the subject.

30. A system for determining a prognosis for a subject with oropharyngeal carcinoma, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to determine the prognosis of the oropharyngeal cancer in the subject.

31. A system for determining a prognosis for a subject with oropharyngeal carcinoma, the system comprising:one or more mass spectrometry units configured for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the phosphorylated form of the one or more protein biomarkers to determine the prognosis of the oropharyngeal cancer in the subject.

32. A system for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to predict the responsiveness of the oropharyngeal cancer to the treatment.

33. A system for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the system comprising: one or more mass spectrometry units configured for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the one or more protein biomarkers to predict the responsiveness of the oropharyngeal cancer to the treatment.

34. A system for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the system comprising:one or more mass spectrometry units configured for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof; and a processing unit configured for using or analysing the expression level of the phosphorylated form of the one or more protein biomarkers to predict the responsiveness of the oropharyngeal cancer to the treatment.

35. A kit for determining the prognosis of a subject with oropharyngeal carcinoma, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, D0K3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA-DPA1, HLA- DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

36. A kit for determining the prognosis of a subject with oropharyngeal carcinoma, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof.

37. A kit for determining the prognosis of a subject with oropharyngeal carcinoma, the kit comprising one or more reagents for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

38. A kit for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACP2, AGA, BORCS6, COL8A1, DOK3, ETHE1, FNBP1, GOLGA3, GSTO1, HAPLN3, HLA- DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof.

39. A kit for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the kit comprising one or more reagents for determining an expression level of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB 1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof.

40. A kit for predicting the responsiveness of an oropharyngeal carcinoma in a subject to a treatment, the kit comprising one or more reagents for determining an expression level of a phosphorylated form of one or more protein biomarkers in one or a plurality of cancer cells, tissues or organs obtained from the subject, wherein the one or more protein biomarkers are selected from the group consisting of ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

41. The kit of any one of Claims 35 to 40, wherein the one or more reagents comprise one or more probes, each probe being specific or selective for one of the one or more protein biomarkers.

42. The kit of Claim 41, wherein each probe is a set of primers, a labelled nucleic acid probe, a labelled protein, a labelled peptide, an aptamer, an antibody and / or an antibody fragment.

43. The method of any one of Claims 1 to 28, the system of any one of Claims 29 to 34 or the kit of any one of Claims 35 to 42, wherein the oropharyngeal cancer is Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC).

44. The method, system or kit of any one of the preceding claims, wherein the one or more protein biomarkers comprises two or more protein biomarkers, three or more protein biomarkers, four or more protein biomarkers or five or more protein biomarkers selected from the group consisting of: (a) ACP2, AGA, BORCS6, C0L8A1, D0K3, ETHE1, FNBP1, G0LGA3, GSTO1,HAPLN3, HLA-DPA1, HLA-DRB4, IGHM, ITIH2, IVL, MGST2, PSMG1, STAG1, TAP2 and UGDH, or a fragment, variant or derivative thereof;(b) AGRN, ALDOA, ARL6IP5, ATP2A2, CDS2, CNDP2, CTSZ, DECR1, ERP29, ETHE1, GAPVD1, GARS1, HLA-A, KRT17, LAP3, LMNB1, MMP2, MVP, NOP56, OPA3, PSMB4, S100A4, SPRR3, STAG1, TCEA1 and WDR81, or a fragment, variant or derivative thereof; or(c) ACTB, ATP5F1B, ATP5F1D, CDKN2A, DARS2, EMILIN1, ENO1, EPPK1, FN1, GNAI3, GNL1, GSR, IGKV1-6, KRT6C, MUC5B, MYH11, OXCT1, PKP2, POSTN, PRKDC, PTBP1, PTBP3, RPS4X, SIK3, STAU1 and TNC, or a fragment, variant or derivative thereof.

45. The system or kit of any one of Claims 29 to 44, for use in the method of any one of Claims 1 to 28.

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