Lung cancer detection proteins and methods of use thereof

Abstract

Methods of evaluating a subject for non-small cell lung cancer (NSCLC) or detecting NSCLC in a subject, the methods comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, from Table 2, or from Table 3. Also, methods of evaluating a subject for small cell lung cancer (SCLC) or detecting SCLC in a subject, the methods comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, from Table 5, or from Table 6. Further, methods of evaluating a subject for lung cancer that is either NSCLC or SCLC, or detecting lung cancer in a subject, the methods comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, from Table 8, or from Table 9.

Description

TITLELUNG CANCER DETECTION PROTEINS AND METHODS OF USE THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of U.S. Provisional Application No. 63 / 616,315, filed on December 29, 2023, which is incorporated herein by reference in its entirety.BACKGROUND

[0002] In both the U.S. and worldwide, lung cancer remains the leading cause of cancer-related deaths (American Cancer Society, 2023; Sung et al., 2021). In the U.S. alone, for 2023, the estimated of new cases is over 238,000, and the estimated number of deaths due to lung cancer is over 127,000 (Siegel et al., 2023).

[0003] There are primarily two types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most prevalent type of lung cancer, accounting for approximately 81% of all lung cancers, while SCLC accounts for 14% of lung cancer cases (American Cancer Society, 2023).

[0004] Early diagnosis for lung cancer has a significant impact on survival rate. According to the American Cancer Society, five-year survival rate of male patients with NSCLC decreases from 59% if diagnosed at the localized stage (z.e., no sign that the cancer has spread outside the lung, approximately Stage I), to 33% if the cancer is at the regional stage (z.e., cancer has spread from the lung to nearby structures or lymph nodes, approximately Stage II / III), and to 7% if the cancer is at the distant stage (z.e., cancer has spread to distant parts of the body, approximately Stage IV) (zt ). A similar trend is seen in female patients, in which the five-year survival rate decreases from 70% to 43% to 11% if diagnose occurs at the localized stage, regional stage, and distant stage, respectively (zt ). For male patients with SCLC, five-year survival rate decreases from 32% if diagnosed at the localized stage, to 17% if the cancer is at the regional stage, and to 2% if the cancer is at the distant stage (zz ). Female patients with SCLC exhibit a similar decrease in five-year survival rate based on the stage of diagnosis (29%, 18%, and 4% if diagnosed at the localized stage, regional stage, and distant stage, respectively) (id.).

[0005] Unfortunately, poor diagnosis has contributed to the high mortality rate associated with lung cancer, as most patients (>75%) have either Stage III or Stage IV lung cancer at diagnosis, and over two-thirds of patients have regional lymph node involvement or distant disease at the time of presentation (Nooreldeen & Bach, 2021). Historically, the only diagnostic tests available for detecting lung cancer in its early stages were chest radiography and sputum cytology, but both tests can be expensive as well as unreliable, having failed in clinical trials and unable to demonstrate efficacy as mass screening tools (Manser et cd.. 2013).

[0006] Therefore, there is an urgent unmet clinical need to improve the detection and diagnosis of both NSCLC and SCLC.SUMMARY OF THE INVENTION

[0007] Some of the main aspects of the present invention are summarized below. Additional aspects are described in the Detailed Description of the Invention, Examples, Drawings, and Claims sections of this disclosure. The description in each section of this disclosure is intended to be read in conjunction with the other sections. Furthermore, the various embodiments described in each section of this disclosure can be combined in various different ways, and all such combinations are intended to fall within the scope of the present invention.

[0008] One aspect of the invention relates to a method of evaluating a subject for NSCLC, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3. In some embodiments, the method further comprises applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having NSCLC. In some embodiments, the method further comprises administering a treatment to the subject.

[0009] Another aspect of the invention relates to a method of treating NSCLC in a subject, comprising acquiring results from a method of evaluating a subject for NSCLC as described herein, and administering a treatment to the subject.

[0010] Another aspect of the invention relates to a method of detecting NSCLC in a subject, the method comprising determining in a biological sample from the subject aconcentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.

[0011] Yet another aspect of the invention relates to a method of treating NSCLC in a subject, comprising acquiring results from a method of detecting NSCLC in a subject as described herein, and administering a treatment to the subject.

[0012] Another aspect of the invention relates to a method of treating NSCLC in a subject in whom NSCLC was detected, the method comprising administering a treatment for NSCLC to the subject, in which NSCLC was detected in the subject by a method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.

[0013] In some embodiments, the NSCLC is early-stage.

[0014] In some embodiments, the subject is asymptomatic of NSCLC.

[0015] Another aspect of the invention relates to a method of evaluating a treatment for NSCLC in a subject, the method comprising administering a treatment for NSCLC, and determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3.

[0016] Another aspect of the invention relates to a method of evaluating the efficacy of a treatment for NSCLC in a subject, the method comprising administering a treatment for NSCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3.

[0017] Another aspect of the invention relates to a method of treating NSCLC in a subject, the method comprising administering a treatment for NSCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.

[0018] Another aspect of the invention relates to a method of adjusting a treatment for NSCLC in a subject, the method comprising administering a treatment for NSCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 1, or from Table 2, or from Table 3.

[0019] Yet another aspect of the invention relates to a method of treating NSCLC in a subject, the method comprising administering a treatment for NSCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.

[0020] Another aspect of the invention relates to a method of monitoring for NSCLC recurrence in a subject, the method comprising administering a treatment for NSCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3. In some embodiments, the method further comprises administering an adjusted treatment when it is determined that the treatment requires adjustment.

[0021] Another aspect of the invention relates to a method of treating NSCLC in a subject, the method comprising administering a treatment for NSCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3. In some embodiments, the method further comprises administering a second treatment when it is determined that the cancer is recurring.

[0022] In some embodiments, the one or more proteins are selected from Table l.A, Table l.B, Table l.C, Table l.D, Table l.E, or Table l.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table LG.

[0023] In some embodiments, the subject is female. In such embodiments, the one or more proteins are selected from Table 2. In some embodiments, the one or more proteins are selected from Table 2.A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 2.G

[0024] In some embodiments, the subject is male. In such embodiments, the one or more proteins are selected from Table 3. In some embodiments, the one or more proteins are selected from Table 3.A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 3.G

[0025] One aspect of the invention relates to a method of evaluating a subject for SCLC, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6. In some embodiments, the method further comprises applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having SCLC. In some embodiments, the method further comprises administering a treatment to the subject.

[0026] Another aspect of the invention relates to a method of treating SCLC in a subject, comprising acquiring results from a method of evaluating a subject for SCLC as described herein, and administering a treatment to the subject.

[0027] Another aspect of the invention relates to a method of detecting SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.

[0028] Yet another aspect of the invention relates to a method of treating SCLC in a subject, comprising acquiring results from a method of detecting SCLC in a subject as described herein, and administering a treatment to the subject.

[0029] Another aspect of the invention relates to a method of treating SCLC in a subject in whom SCLC was detected, the method comprising administering a treatment for SCLC to the subject, in which SCLC was detected in the subject by a method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.

[0030] In some embodiments, the SCLC is early-stage.

[0031] In some embodiments, the subject is asymptomatic of SCLC.

[0032] Another aspect of the invention relates to a method of evaluating a treatment for SCLC in a subject, the method comprising administering a treatment for SCLC, and determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6.

[0033] Another aspect of the invention relates to a method of evaluating the efficacy of a treatment for SCLC in a subject, the method comprising administering a treatment for SCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6.

[0034] Another aspect of the invention relates to a method of treating SCLC in a subject, the method comprising administering a treatment for SCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.

[0035] Another aspect of the invention relates to a method of adjusting a treatment for SCLC in a subject, the method comprising administering a treatment for SCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 4, or from Table 5, or from Table 6

[0036] Yet another aspect of the invention relates to a method of treating SCLC in a subject, the method comprising administering a treatment for SCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.

[0037] Another aspect of the invention relates to a method of monitoring for SCLC recurrence in a subject, the method comprising administering a treatment for SCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6. In some embodiments,the method further comprises administering an adjusted treatment when it is determined that the treatment requires adjustment.

[0038] Another aspect of the invention relates to a method of treating SCLC in a subject, the method comprising administering a treatment for SCLC to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6. In some embodiments, the method further comprises administering a second treatment when it is determined that the cancer is recurring.

[0039] In some embodiments, the one or more proteins are selected from Table 4.A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 4.G.

[0040] In some embodiments, the subject is female. In such embodiments, the one or more proteins are selected from Table 5. In some embodiments, the one or more proteins are selected from Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 5.G

[0041] In some embodiments, the subject is male. In such embodiments, the one or more proteins are selected from Table 6. In some embodiments, the one or more proteins are selected from Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 6.G

[0042] One aspect of the invention relates to a method of evaluating a subject for lung cancer, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9. In some embodiments, the method further comprises applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having lung cancer. The lung cancer may be either NSCLC or SCLC. In some embodiments, the method further comprises administering a treatment to the subject.

[0043] Another aspect of the invention relates to a method of treating lung cancer in a subject, comprising acquiring results from a method of evaluating a subject for lung cancer as described herein, and administering a treatment to the subject.

[0044] Another aspect of the invention relates to a method of detecting lung cancer in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.

[0045] Yet another aspect of the invention relates to a method of treating lung cancer in a subject, comprising acquiring results from a method of detecting lung cancer in a subject as described herein, and administering a treatment to the subject.

[0046] Another aspect of the invention relates to a method of treating lung cancer in a subject in whom lung cancer was detected, the method comprising administering a treatment for lung cancer to the subject, in which lung cancer was detected in the subject by a method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.

[0047] In some embodiments, the lung cancer is early-stage.

[0048] In some embodiments, the subject is asymptomatic of lung cancer.

[0049] Another aspect of the invention relates to a method of evaluating a treatment for lung cancer in a subject, the method comprising administering a treatment for lung cancer, and determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9.

[0050] Another aspect of the invention relates to a method of evaluating the efficacy of a treatment for lung cancer in a subject, the method comprising administering a treatment for lung cancer to the subject, and determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9

[0051] Another aspect of the invention relates to a method of treating lung cancer in a subject, the method comprising administering a treatment for lung cancer to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.

[0052] Another aspect of the invention relates to a method of adjusting a treatment for lung cancer in a subject, the method comprising administering a treatment for lung cancer to the subject, and determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 7, or from Table 8, or from Table 9.

[0053] Yet another aspect of the invention relates to a method of treating lung cancer in a subject, the method comprising administering a treatment for lung cancer to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.

[0054] Another aspect of the invention relates to a method of monitoring for lung cancer recurrence in a subject, the method comprising administering a treatment for lung cancer to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9. In some embodiments, the method further comprises administering an adjusted treatment when it is determined that the treatment requires adjustment.

[0055] Another aspect of the invention relates to a method of treating lung cancer in a subject, the method comprising administering a treatment for lung cancer to the subject, and determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9. In some embodiments, the method further comprises administering a second treatment when it is determined that the cancer is recurring.

[0056] In some embodiments, the one or more proteins are selected from Table 7.A, Table 7.B, Table 7.C, Table 7.D, Table 7.E, or Table 7.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 7.G.

[0057] In some embodiments, the subject is female. In such embodiments, the one or more proteins are selected from Table 8. In some embodiments, the one or more proteins are selected from Table 8.A, Table 8.B, Table 8.C, Table 8.D, Table 8.E, or Table 8.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 2.G

[0058] In some embodiments, the subject is male. In such embodiments, the one or more proteins are selected from Table 9. In some embodiments, the one or more proteins are selected from Table 9.A, Table 9.B, Table 9.C, Table 9.D, Table 9.E, or Table 9.F. In certain embodiments, the one or more proteins comprise at least the proteins set forth in Table 9.G

[0059] In embodiments of the invention, the biological sample is selected from a plasma sample, serum sample, saliva sample, cerebral spinal fluid (CSF) sample, sweat sample, urine sample, or tear sample.

[0060] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 1. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 1.A, Table l.B, Table l.C, Table l.D, Table l.E, or Table l.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table l.G.

[0061] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 2. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 2.A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 2.G.

[0062] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 3. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 3.A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 3.G.

[0063] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 4. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 4.A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 4.G.

[0064] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 5. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 5.G.

[0065] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 6. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 6.G.

[0066] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 7. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 7.A, Table 7.B, Table 7.C, Table 7.D, Table 7.E, or Table 7.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 7.G.

[0067] Another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 8. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 8.A, Table 8.B, Table 8.C, Table 8.D, Table 8.E, or Table 8.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 8.G.

[0068] In yet, another aspect of the invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 9. In some embodiments, the method comprises determining individual amounts of one or more proteins selected from Table 9.A, Table 9.B, Table 9.C, Table 9.D, Table 9.E , or Table 9.F. In some embodiments, the method comprises determining individual amounts of at least the proteins of Table 9.G.

[0069] Another aspect of the invention relates to a kit comprising one or more components that can be used to perform assays for detecting one or more proteins of Table 1, or one or more proteins of Table 2, or one or more proteins of Table 3, or one or more proteins of Table 4, or one or more proteins of Table 5, or one or more proteins of Table 6, or one or more proteins of Table 7, or one or more proteins of Table 8, or one or more proteins of Table 9.BRIEF DESCRIPTION OF THE FIGURES

[0070] FIG. 1 shows accuracy, measured as area-under-the-curve (AUC) of a receiver operating characteristic (ROC) curve, of detecting NSCLC in subjects using random combinations of two to 15 proteins selected from Table 1.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0071] FIG. 2 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 161 proteins listed in Table l.A, as described in the Example.

[0072] FIG. 3 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 75 proteins listed in Table l.B, as described in the Example.

[0073] FIG. 4 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 30 proteins listed in Table l.C, as described in the Example.

[0074] FIG. 5 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 50 proteins listed in Table l.D, as described in the Example.

[0075] FIG. 6 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 50 proteins listed in Table l.E, as described in the Example.

[0076] FIG. 7 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 54 proteins listed in Table l.F, as described in the Example.

[0077] FIG. 8 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a subject using a panel of the 9 proteins listed in Table l.G, as described in the Example.

[0078] FIG. 9 shows accuracy, measured as AUC of a ROC curve, of detecting NSCLC in female subjects using random combinations of two to 15 proteins selected from Table 2.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0079] FIG. 10 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in female subjects using a panel of the 95 proteins listed in Table 2.A, as described in the Example.

[0080] FIG. 11 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a female subjects using a panel of the 43 proteins listed in Table 2.B, as described in the Example.

[0081] FIG. 12 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a female subjects using a panel of the 30 proteins listed in Table 2.C, as described in the Example.

[0082] FIG. 13 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a female subjects using a panel of the 53 proteins listed in Table 2.D, as described in the Example.

[0083] FIG. 14 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a female subjects using a panel of the 50 proteins listed in Table 2.E, as described in the Example.

[0084] FIG. 15 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a female subjects using a panel of the 32 proteins listed in Table 2.F, as described in the Example.

[0085] FIG. 16 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a female subjects using a panel of the 14 proteins listed in Table 2.G, as described in the Example.

[0086] FIG. 17 shows accuracy, measured as AUC of a ROC curve, of detecting NSCLC in male subjects using random combinations of two to 15 proteins selected from Table 3.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0087] FIG. 18 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in male subjects using a panel of the 99 proteins listed in Table 3.A, as described in the Example.

[0088] FIG. 19 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a male subjects using a panel of the 34 proteins listed in Table 3.B, as described in the Example.

[0089] FIG. 20 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a males subjects using a panel of the 30 proteins listed in Table 3.C, as described in the Example.

[0090] FIG. 21 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a males subjects using a panel of the 50 proteins listed in Table 3.D, as described in the Example.

[0091] FIG. 22 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a males subjects using a panel of the 50 proteins listed in Table 3.E, as described in the Example.

[0092] FIG. 23 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a males subjects using a panel of the 33 proteins listed in Table 3.F, as described in the Example.

[0093] FIG. 24 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting NSCLC in a males subjects using a panel of the 19 proteins listed in Table 3.G, as described in the Example.

[0094] FIG. 25 shows accuracy, measured as AUC of a ROC curve, of detecting SCLC in subjects using random combinations of two to 15 proteins selected from Table 4.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0095] FIG. 26 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility ofdetecting SCLC in a subject using a panel of the 112 proteins listed in Table 4. A, as described in the Example.

[0096] FIG. 27 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a subject using a panel of the 3 proteins listed in Table 4.B, as described in the Example.

[0097] FIG. 28 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a subject using a panel of the 30 proteins listed in Table 4.C, as described in the Example.

[0098] FIG. 29 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a subject using a panel of the 51 proteins listed in Table 4.D, as described in the Example.

[0099] FIG. 30 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a subject using a panel of the 51 proteins listed in Table 4.E, as described in the Example.

[0100] FIG. 31 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a subject using a panel of the 37 proteins listed in Table 4.F, as described in the Example.

[0101] FIG. 32 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a subject using a panel of the 4 proteins listed in Table 4.G, as described in the Example.

[0102] FIG. 33 shows accuracy, measured as AUC of a ROC curve, of detecting SCLC in female subjects using random combinations of two to 15 proteins selected from Table 5.A, as described in the Example. The process of selecting the random combinationsof each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0103] FIG. 34 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in female subjects using a panel of the 106 proteins listed in Table 5.A, as described in the Example.

[0104] FIG. 35 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a female subjects using a panel of the 5 proteins listed in Table 5.B, as described in the Example.

[0105] FIG. 36 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a female subjects using a panel of the 30 proteins listed in Table 5.C, as described in the Example.

[0106] FIG. 37 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a female subjects using a panel of the 50 proteins listed in Table 5.D, as described in the Example.

[0107] FIG. 38 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a female subjects using a panel of the 52 proteins listed in Table 5.E, as described in the Example.

[0108] FIG. 39 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a female subjects using a panel of the 35 proteins listed in Table 5.F, as described in the Example.

[0109] FIG. 40 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a female subjects using a panel of the 7 proteins listed in Table 5.G, as described in the Example.

[0110] FIG. 41 shows accuracy, measured as AUC of a ROC curve, of detecting SCLC in male subjects using random combinations of two to 15 proteins selected from Table 6.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0111] FIG. 42 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in male subjects using a panel of the 92 proteins listed in Table 6. A, as described in the Example.

[0112] FIG. 43 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a male subjects using a panel of the 10 proteins listed in Table 6.B, as described in the Example.

[0113] FIG. 44 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a males subjects using a panel of the 30 proteins listed in Table 6.C, as described in the Example.

[0114] FIG. 45 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a males subjects using a panel of the 50 proteins listed in Table 6.D, as described in the Example.

[0115] FIG. 46 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a males subjects using a panel of the 50 proteins listed in Table 6.E, as described in the Example.

[0116] FIG. 47 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting SCLC in a males subjects using a panel of the 31 proteins listed in Table 6.F, as described in the Example.

[0117] FIG. 48 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility ofdetecting SCLC in a males subjects using a panel of the 13 proteins listed in Table 6.G, as described in the Example.

[0118] FIG. 49 shows accuracy, measured as AUC of a ROC curve, of detecting lung cancer (either NSCLC or SCLC) in subjects using random combinations of two to 15 proteins selected from Table 7.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc.) was performed for 1000 iterations.

[0119] FIG. 50 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 130 proteins listed in Table 7.A, as described in the Example.

[0120] FIG. 51 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 73 proteins listed in Table 7.B, as described in the Example.

[0121] FIG. 52 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 30 proteins listed in Table 7.C, as described in the Example.

[0122] FIG. 53 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 51 proteins listed in Table 7.D, as described in the Example.

[0123] FIG. 54 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 50 proteins listed in Table 7.E, as described in the Example.

[0124] FIG. 55 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility ofdetecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 43 proteins listed in Table 7.F, as described in the Example.

[0125] FIG. 56 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a subject using a panel of the 12 proteins listed in Table 7.G, as described in the Example.

[0126] FIG. 57 shows accuracy, measured as AUC of a ROC curve, of detecting lung cancer (either NSCLC or SCLC) in female subjects using random combinations of two to 15 proteins selected from Table 8.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc. was performed for 1000 iterations.

[0127] FIG. 58 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in female subjects using a panel of the 92 proteins listed in Table 8.A, as described in the Example.

[0128] FIG. 59 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a female subjects using a panel of the 28 proteins listed in Table 8.B, as described in the Example.

[0129] FIG. 60 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a female subjects using a panel of the 30 proteins listed in Table 8.C, as described in the Example.

[0130] FIG. 61 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a female subjects using a panel of the 51 proteins listed in Table 8.D, as described in the Example.

[0131] FIG. 62 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility ofdetecting lung cancer (either NSCLC or SCLC) in a female subjects using a panel of the 51 proteins listed in Table 8.E, as described in the Example.

[0132] FIG. 63 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a female subjects using a panel of the 31 proteins listed in Table 8.F, as described in the Example.

[0133] FIG. 64 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a female subjects using a panel of the 18 proteins listed in Table 8.G, as described in the Example.

[0134] FIG. 65 shows accuracy, measured as AUC of a ROC curve, of detecting lung cancer (either NSCLC or SCLC) in male subjects using random combinations of two to 15 proteins selected from Table 9.A, as described in the Example. The process of selecting the random combinations of each number of proteins (two proteins, three proteins, etc. was performed for 1000 iterations.

[0135] FIG. 66 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in male subjects using a panel of the 90 proteins listed in Table 9.A, as described in the Example.

[0136] FIG. 67 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a male subjects using a panel of the 29 proteins listed in Table 9.B, as described in the Example.

[0137] FIG. 68 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a males subjects using a panel of the 30 proteins listed in Table 9.C, as described in the Example.

[0138] FIG. 69 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility ofdetecting lung cancer (either NSCLC or SCLC) in a males subjects using a panel of the 51 proteins listed in Table 9.D, as described in the Example.

[0139] FIG. 70 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a males subjects using a panel of the 50 proteins listed in Table 9.E, as described in the Example.

[0140] FIG. 71 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a males subjects using a panel of the 30 proteins listed in Table 9.F, as described in the Example.

[0141] FIG. 72 shows ROC curves generated by application of the first classifer (Panel A) and of the second classifier (Panel B), which depicts the high diagnostic utility of detecting lung cancer (either NSCLC or SCLC) in a males subjects using a panel of the 13 proteins listed in Table 9.G, as described in the Example.DETAILED DESCRIPTION OF THE INVENTION

[0142] The practice of the present invention can employ, unless otherwise indicated, conventional techniques of proteomics, bioinformatics, oncology, and pharmacology, which are within the skill of the art.

[0143] In order that the present invention can be more readily understood, certain terms are first defined. Additional definitions are set forth throughout the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention is related.

[0144] Any headings provided herein are not limitations of the various aspects or embodiments of the invention, which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.

[0145] All references cited in this disclosure are hereby incorporated by reference in their entireties. In addition, any manufacturers’ instructions or catalogues for any products cited or mentioned herein are incorporated by reference. Documents incorporated byreference into this text, or any teachings therein, can be used in the practice of the present invention. Documents incorporated by reference into this text are not admitted to be prior art.Definitions

[0146] The phraseology or terminology in this disclosure is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance.

[0147] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents, unless the context clearly dictates otherwise. The terms “a” (or “an”) as well as the terms “one or more” and “at least one” can be used interchangeably.

[0148] Furthermore, “and / or” is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term “and / or” as used in a phrase such as “A and / or B” is intended to include A and B, A or B, A (alone), and B (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to include A, B, and C; A, B, or C; A or B; A or C; B or C; A and B; A and C; B and C; A (alone); B (alone); and C (alone).

[0149] Units, prefixes, and symbols are denoted in their Systeme International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range, and any individual value provided herein can serve as an endpoint for a range that includes other individual values provided herein. For example, a set of values such as 1, 2, 3, 8, 9, and 10 is also a disclosure of a range of numbers from 1-10. Where a numeric term is preceded by “about,” the term includes the stated number and values ±10% of the stated number. The headings provided herein are not limitations of the various aspects or embodiments of the invention, which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.

[0150] Wherever embodiments are described with the language “comprising,” otherwise analogous embodiments described in terms of “consisting of’ and / or “consisting essentially of’ are included.

[0151] An “effective amount” of a composition as disclosed herein is an amount sufficient to carry out a specifically stated purpose. An “effective amount” can be determined empirically and in a routine manner, in relation to the stated purpose, route of administration, and dosage form.

[0152] The term “subject” or “individual” or “patient” means any subject, preferably a mammalian subject, for whom diagnosis, prognosis, or therapy is desired. Mammalian subjects include humans, domestic animals, farm animals, sports animals, and zoo animals including, e.g., humans, non-human primates, dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, and so on.

[0153] The term “early-stage” in the context of cancer (e.g., “early-stage cancer” or cancer that “is early-stage”) refers generally to a level of advancement of the cancer prior to the cancer spreading to lymph nodes or tissues that are distant from the tissue of origin. In some embodiments, an early-stage cancer can refer to a cancer that is a Stage 0, Stage I, or Stage II cancer, based on the stage classification known in the art that grades cancer from Stage 0 (e.g., carcinoma in situ, where the cancer is still only in the layer of cells where it started and has not advanced farther), through Stages I-III (e.g., cancer is present — the higher the number, the larger the tumor and the more it has spread into nearby tissues), and to Stage IV (e.g., the cancer has spread to distant parts of the body). In some embodiments, this stage classification incorporates the TNM System, which evaluates the cancer based on the size and extent of the main tumor (“T”), the number of nearby lymph nodes that have cancer (“N”), and the extent to which the cancer has metastasized (“M”).

[0154] The term “symptomatic” means to exhibit one or more signs or features that are regarded as indicative, or are known to be associated with, a disease or condition. A subject may be considered as “symptomatic” of cancer based on symptoms that are known in the art to be associated with cancer in general or for specific types of cancer. Examples include, but are not limited to, fatigue; lump or area of thickening that can be felt under the skin; weight changes, including unintended loss or gain; skin changes, such as yellowing, darkening, or redness of the skin, sores that will not heal, or changes to existing moles; changes in bowel or bladder habits; persistent cough or trouble breathing; difficulty swallowing; hoarseness; persistent indigestion or discomfort after eating; persistent, unexplained muscle or joint pain; persistent, unexplained fevers or night sweats; andunexplained bleeding or bruising. Symptoms that can occur with NSCLC in particular include, but are not limited to, a new cough that lasts or gets worse; chest pain, including pain that hurts more when coughing, laughing, or taking deep breaths; hoarseness or change in voice; harsh, raspy sounds when breathing; wheezing; weight loss and / or little appetite; coughing up blood or mucus; shortness of breath; feeling weak or tired; lasting lung problems such as bronchitis or pneumonia; bone pain; dizziness or balance problems; numbness or weakness in arm or leg; yellow skin or yellow eyes; and headache.

[0155] A subject may be considered as “suspected of having a cancer” due to the presence of symptoms, z.e., the subject is symptomatic; genetic markers; patient’s habits or medical history; patient’s family medical history; examination or tests known in the art for which the outcome is associated with cancer or risk of cancer, etc.

[0156] The term “asymptomatic” means to not exhibit any signs or features that are regarded as indicative, or are known to be associated with, a disease or condition.

[0157] Terms such as “treating” or “treatment” or “to treat” or “alleviating” or “to alleviate” refer to therapeutic measures that cure, slow down, lessen symptoms of, and / or halt progression of a diagnosed pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder. In certain embodiments, a subject is successfully “treated” for a disease or disorder if the patient shows, e.g., total, partial, or transient alleviation or elimination of symptoms associated with the disease or disorder.

[0158] The term “ROC” or “ROC curve” is used to refer to a receiver operator characteristic curve. A ROC curve can be a graphical representation of the performance of a classifier system. For any given method, a ROC can be generated by plotting the sensitivity against the specificity. The sensitivity and specificity of a method for detecting the presence of a cancer or a specific type of cancer can be determined at various concentrations of proteins in a sample from the subject. The AUC of a ROC curve is a metric that can provide a measure of diagnostic utility of a method, taking into account both the sensitivity and specificity of the method. The AUC can range from 0.5 to 1.0, where a value closer to 0.5 can indicate that the method has limited diagnostic utility (e.g., lower sensitivity and / or specificity) and a value closer to 1.0 indicates the method has greater diagnostic utility (e.g., higher sensitivity and / or specificity).

[0159] The term “third party” means a person or group different from the two persons or groups primarily involved. For example, in a multi-step method involving a subject, a third party can be a person / group other than the subject and the person / group primarily responsible for the performance of the steps. In such an example, a third party may perform one of the steps in the method. As another example, in a treatment method involving administration of a treatment to a subject, a third party may be a person / group other than the subject and the person / group administering the treatment.

[0160] The term “cancer recurrence” refers to a return of cancer after a period of remission. The cancer can reappear in the same, or close to, the place that it was previously found (local recurrence); in the lymph nodes and tissue located in the vicinity of the original cancer (regional recurrence); or in areas farther away from the original cancer (distant recurrence).Methods of the Invention

[0161] The present invention involves the use of proteins in the detection or evaluation of NSCLC in subjects (also referred to herein as “NSCLC detection proteins”), of SCLC in subjects (also referred to herein as “SCLC detection proteins”), or lung cancer that may be either NSCLC or SCLC in subjects (also referred to herein as “general lung cancer detection proteins”). Such use can be applied in methods of evaluating a subject for NSCLC, SCLC, or lung cancer; methods of treating subjects for NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC; among others.

[0162] The proteins can be used to detect or evaluate NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC, based on a biological sample from the subject. The biological sample may be any biological sample capable of being obtained from the subject, and encompass fluids, solids, tissues, and gases. In some embodiments, the sample may be a blood product, such as plasma, serum, and the like. In some embodiments, the sample may be a urine sample, saliva sample, CSF sample, sweat sample, or tear sample. In preferred embodiments, the biological sample is advantageously a plasma sample.

[0163] An aspect of the present invention relates to a method of evaluating a subject for a cancer that is associated with the lung; or a method of evaluating a subject for NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC. The method comprises determining in a biological sample from the subject a concentration of one or more proteinsselected from Table 1, or from Table 2, or from Table 3, or from Table 4, or from Table 5, or from Table 6, or from Table 7, or from Table 8, or from Table 9.

[0164] In preferred embodiments, the sample is already separated / obtained / collected from the subject at the time of the evaluation. In some embodiments, the sample is separated from the subject at home and / or by the subject prior to the evaluation. In some embodiments, the method further comprises obtaining a biological sample from the subject.

[0165] In embodiments of the invention, the method identifies whether the subject has NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC. The method may further comprise applying a classifier to the concentration of the one or more proteins. The classifier identifies whether the concentration of the one or more proteins is indicative that the subject has NSCLC, has SCLC, or has a lung cancer that may be either NSCLC or SCLC.

[0166] In embodiments of the invention, the methods of evaluating a subject further comprise administering a treatment. In some embodiments, the treatment is administered when it is determined that the subject has NSCLC, that the subject has SCLC, or that the subject has lung cancer that may be either NSCLC or SCLC.

[0167] To this end, an aspect of the present invention relates to a method of treating NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC, in a subject. The method comprises (a) acquiring results from methods of evaluating a subject for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC, as described herein, and (b) administering a treatment to the subject. In some embodiments, the results from methods of evaluating a subject for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC, are provided by a third party. In some embodiments, the treatment is responsive to the results, e.g., responsive to having NSCLC, to having SCLC, or to having lung cancer that may be either NSCLC or SCLC.

[0168] Another aspect of the present invention relates to a method of treating NSCLC in a subject, in which the method comprises (a) acquiring results from an evaluation of the subject that determined the subject has NSCLC; (b) administering a treatment to the subject, e.g., a treatment for NSCLC, in which the evaluation comprises: (I) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3, and (II) applying a classifier to the concentrationof the one or more proteins to identify whether the subject has NSCLC. In some embodiments, the results in (a) are acquired from a third party.

[0169] An aspect of the present invention relates to a method of detecting NSCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.

[0170] In embodiments of the invention, the method of detecting NSCLC in a subject further comprises administering a treatment. In some embodiments, the treatment is administered when NSCLC is detected.

[0171] To this end, an aspect of the present invention relates to a method of treating NSCLC in a subject, comprising (a) acquiring results from a method of detecting NSCLC in a subject as described herein, and (b) administering a treatment to the subject. In some embodiments, the results from the method of detecting NSCLC in a subject are provided by a third party. In some embodiments, the treatment is responsive to the results, e.g., responsive to NSCLC being detected.

[0172] An aspect of the invention relates to a method of treating NSCLC in a subject in whom NSCLC was detected, the method comprising administering a treatment for the NSCLC; in which the NSCLC had been detected in the subject by a method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3, and applying a classifier to the concentration of the one or more proteins to identify whether the subject has NSCLC. In some embodiments, the method of detecting the NSCLC was performed by a third party.

[0173] Yet another aspect of the present invention relates to a method of treating NSCLC in a subject, in which the method comprises (a) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; (b) applying a classifier to the concentration of the one or more proteins to identify that the subject has NSCLC; and (c) administering a treatment to the subject, e.g., a treatment for NSCLC.

[0174] Another aspect of the present invention relates to a method of treating cancer in a patient who has been or was determined to have NSCLC, comprising administering atreatment for NSCLC to the patient, in which the patient was determined to have NSCLC by a method comprising (a) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3, and (b) applying a classifier to the concentration of the one or more proteins. The classifier identifies whether the concentration of the one or more proteins is indicative that the subject has NSCLC.

[0175] In some embodiments, the subject is asymptomatic for NSCLC. In some embodiments, the methods may be performed as part of, or may be included within, or may overlap with, a screening for NSCLC in the subject. In some embodiments, the subject is undergoing a screen for NSCLC.

[0176] In some embodiments, the subject is suspected of having NSCLC, such as symptomatic of having NSCLC.

[0177] In addition, an aspect of the present invention relates to a method of evaluating a treatment for NSCLC in a subject. The method comprises (a) administering a treatment for NSCLC, and (b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3. In preferred embodiments, the sample is already separated / obtained from the subject at the time of performing (b). In some embodiments, administration of the treatment in (a) may be performed by a third party. In other embodiments, determining the concentration of the one or more proteins in (b) may be performed by a third party.

[0178] In embodiments of the invention, the one or more proteins identifies whether the subject has NSCLC after treatment. Thus, the method may further comprise applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having NSCLC.

[0179] Another aspect of the present invention relates to a method of treating SCLC in a subject, in which the method comprises (a) acquiring results from an evaluation of the subject that determined the subject has SCLC; (b) administering a treatment to the subject, e.g., a treatment for SCLC, in which the evaluation comprises: (I) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6, and (II) applying a classifier to the concentration of the oneor more proteins to identify whether the subject has SCLC. In some embodiments, the results in (a) are acquired from a third party.

[0180] An aspect of the present invention relates to a method of detecting SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.

[0181] In embodiments of the invention, the method of detecting SCLC in a subject further comprises administering a treatment. In some embodiments, the treatment is administered when SCLC is detected.

[0182] To this end, an aspect of the present invention relates to a method of treating SCLC in a subject, comprising (a) acquiring results from a method of detecting SCLC in a subject as described herein, and (b) administering a treatment to the subject. In some embodiments, the results from the method of detecting SCLC in a subject are provided by a third party. In some embodiments, the treatment is responsive to the results, e.g., responsive to SCLC being detected.

[0183] An aspect of the invention relates to a method of treating SCLC in a subject in whom SCLC was detected, the method comprising administering a treatment for the SCLC; in which the SCLC had been detected in the subject by a method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6, and applying a classifier to the concentration of the one or more proteins to identify whether the subject has SCLC. In some embodiments, the method of detecting the SCLC was performed by a third party.

[0184] Yet another aspect of the present invention relates to a method of treating SCLC in a subject, in which the method comprises (a) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; (b) applying a classifier to the concentration of the one or more proteins to identify that the subject has SCLC; and (c) administering a treatment to the subject, e.g., a treatment for SCLC.

[0185] Another aspect of the present invention relates to a method of treating cancer in a patient who has been or was determined to have SCLC, comprising administering atreatment for SCLC to the patient, in which the patient was determined to have SCLC by a method comprising (a) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6, and (b) applying a classifier to the concentration of the one or more proteins. The classifier identifies whether the concentration of the one or more proteins is indicative that the subject has SCLC.

[0186] In some embodiments, the subject is asymptomatic for SCLC. In some embodiments, the methods may be performed as part of, or may be included within, or may overlap with, a screening for SCLC in the subject. In some embodiments, the subject is undergoing a screen for SCLC.

[0187] In some embodiments, the subject is suspected of having SCLC, such as symptomatic of having SCLC.

[0188] In addition, an aspect of the present invention relates to a method of evaluating a treatment for SCLC in a subject. The method comprises (a) administering a treatment for SCLC, and (b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6. In preferred embodiments, the sample is already separated / obtained from the subject at the time of performing (b). In some embodiments, administration of the treatment in (a) may be performed by a third party. In other embodiments, determining the concentration of the one or more proteins in (b) may be performed by a third party.

[0189] In embodiments of the invention, the one or more proteins identifies whether the subject has SCLC after treatment. Thus, the method may further comprise applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having SCLC.

[0190] Another aspect of the present invention relates to a method of treating lung cancer that may be either NSCLC or SCLC in a subject, in which the method comprises (a) acquiring results from an evaluation of the subject that determined the subject has lung cancer; (b) administering a treatment to the subject, e.g., a treatment for lung cancer, in which the evaluation comprises: (I) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9, and (II) applying a classifier to the concentration of the one or more proteins to identifywhether the subject has lung cancer. In some embodiments, the results in (a) are acquired from a third party.

[0191] An aspect of the present invention relates to a method of detecting lung cancer that may be either NSCLC or SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.

[0192] In embodiments of the invention, the method of detecting lung cancer that may be either NSCLC or SCLC in a subject further comprises administering a treatment. In some embodiments, the treatment is administered when lung cancer is detected.

[0193] To this end, an aspect of the present invention relates to a method of treating lung cancer that may be either NSCLC or SCLC in a subject, comprising (a) acquiring results from a method of detecting lung cancer in a subject as described herein, and (b) administering a treatment to the subject. In some embodiments, the results from the method of detecting lung cancer in a subject are provided by a third party. In some embodiments, the treatment is responsive to the results, e.g., responsive to lung cancer being detected.

[0194] An aspect of the invention relates to a method of treating lung cancer that may be either NSCLC or SCLC in a subject in whom lung cancer was detected, the method comprising administering a treatment for the lung cancer; in which the lung cancer had been detected in the subject by a method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9, and applying a classifier to the concentration of the one or more proteins to identify whether the subject has lung cancer. In some embodiments, the method of detecting the lung cancer was performed by a third party.

[0195] Yet another aspect of the present invention relates to a method of treating lung cancer that may be either NSCLC or SCLC in a subject, in which the method comprises (a) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; (b) applying a classifier to the concentration of the one or more proteins to identify that the subject has lung cancer; and (c) administering a treatment to the subject, e.g., a treatment for lung cancer.

[0196] Another aspect of the present invention relates to a method of treating cancer in a patient who has been or was determined to have lung cancer that may be either NSCLC or SCLC, comprising administering a treatment for lung cancer to the patient, in which the patient was determined to have lung cancer by a method comprising (a) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9, and (b) applying a classifier to the concentration of the one or more proteins. The classifier identifies whether the concentration of the one or more proteins is indicative that the subject has lung cancer.

[0197] In some embodiments, the subject is asymptomatic for lung cancer. In some embodiments, the methods may be performed as part of, or may be included within, or may overlap with, a screening for lung cancer in the subject. In some embodiments, the subject is undergoing a screen for lung cancer.

[0198] In some embodiments, the subject is suspected of having lung cancer, such as symptomatic of having lung cancer.

[0199] In addition, an aspect of the present invention relates to a method of evaluating a treatment for lung cancer that may be either NSCLC or SCLC in a subject. The method comprises (a) administering a treatment for lung cancer, and (b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9. In preferred embodiments, the sample is already separated / obtained from the subject at the time of performing (b). In some embodiments, administration of the treatment in (a) may be performed by a third party. In other embodiments, determining the concentration of the one or more proteins in (b) may be performed by a third party.

[0200] In embodiments of the invention, the one or more proteins identifies whether the subject has lung cancer after treatment. Thus, the method may further comprise applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having lung cancer.

[0201] The treatment may be any known treatment for cancer as known in the art and as described herein. The administration of the treatment in (a) may comprise a single administration or occurrence of a therapy, or may comprise multiple administrations or occurrences of a therapy.

[0202] The determination in a biological sample from the subject a concentration of one or more proteins in (b) may be performed more than once. The determination may overlap with the administration of the treatment in (a) or may occur after the administration of the treatment in (a).

[0203] In embodiments in which determination in a biological sample from the subject a concentration of one or more proteins in (b) is occurring after the administration of the treatment in (a), the determination may occur immediately after the administration of the treatment or a period of time after the administration of the treatment. The period of time may be one day or more, or one week or more, or one month or more, or one year or more; including one day, or two days, or three days, or four days, or five days, or six days, or about one week, or about two weeks, or about three weeks, or about four weeks, or about five weeks, or about six weeks, or about seven weeks, or about eight weeks, or about nine weeks, or about ten weeks, or about 11 weeks, or about 12 weeks, or about one month, or about two months, or about three months, or about four months, or about five months, or about six months, or about seven months, or about eight months, or about nine months, or about ten months, or about 11 months, or about 12 months, or about one year, or about two years, or about three years, or about four years, or about five years, or about six years, or about seven years, or about eight years, or about nine years, or about ten years, or about 11 years, or about 12 years, or about 13 years, or about 14 years, or about 15 years, or about 16 years, or about17 years, or about 18 years, or about 19 years, or about 20 years, or about 21 years, or about22 years, or about 23 years, or about 24 years, or about 25 years, or about 26 years, or about27 years, or about 28 years, or about 29 years, or about 30 years, or more; including any ranges formed with these time periods as endpoints, for examples about 4 weeks to about 13 years, about 7 months to about 3 years, etc.

[0204] In some embodiments, the presence of NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC, after treatment may be indicative that the treatment was not effective. Thus, another aspect of the invention is a method of evaluating the efficacy of a treatment for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC, comprising (a) administering the treatment, and (b) determining in a biological sample from the subject a concentration of one or more proteins, as described herein. Yet another aspect is a method of treatment, comprising (a) administering a treatment for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC, and (b) determining in a biologicalsample from the subject a concentration of one or more proteins, as described herein, to evaluate whether the treatment was effective.

[0205] In some embodiments, the presence of NSCLC, of SCLC, or lung cancer that may be either NSCLC or SCLC, after treatment may be indicative that the treatment requires adjustment. Thus, another aspect of the invention is a method of adjusting a treatment for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC, comprising (a) administering the treatment, and (b) determining in a biological sample from the subject a concentration of one or more proteins, as described herein, to evaluate whether the treatment requires adjustment; such method may further comprise administering a second treatment. The second treatment may be different from the original treatment, for example, a different therapy or different dosage of the same therapy.

[0206] In some embodiments, the presence of NSCLC, or of SCLC, or of lung cancer that may be either NSCLC or SCLC after treatment may be indicative of cancer recurrence. Thus, another aspect of the invention is a method of monitoring for NSCLC recurrence, for SCLC recurrence, or for recurrence of lung cancer that may be either NSCLC or SCLC, comprising (a) administering a treatment for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC; and (b) determining in a biological sample from the subject a concentration of one or more proteins, as described herein. Yet another aspect is a method of treatment, comprising (a) administering a treatment for NSCLC, for SCLC, or for lung cancer that may be either NSCLC or SCLC; and (b) determining in a biological sample from the subject a concentration of one or more proteins, as described herein, to evaluate cancer recurrence. In some embodiments, the method may further comprise administering a second treatment when it is determined that the NSCLC is recurring, that the SCLC is recurring, or that the lung cancer that may be either NSCLC or SCLC is recurring. The second treatment may be different from the original treatment, for example, a different therapy or different dosage of the same therapy.

[0207] An aspect of the present invention relates to a method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 1, from Table 2, from Table 3, from Table 4, from Table 5, from Table 6, from Table 7, from Table 8, or from Table 9. In some embodiments, theindividual amounts of the one or more proteins is determined in a biological sample from the subject.

[0208] In some embodiments, the biological sample is a plasma sample, serum sample, saliva sample, CSF sample, sweat sample, urine sample, or tear sample. In preferred embodiments, the biological sample is a plasma sample.

[0209] In embodiments of the invention, the methods may further comprise obtaining or collecting a biological sample from the subject before determining the concentration of one or more proteins in the biological sample. The collection of the biological sample may be performed in a home (e.g., the home of the subject) or at a medical facility (e.g., doctor’s office, hospital, urgent care center, etc.).

[0210] In some embodiments, the determination of the concentration of one or more proteins in the biological sample may be performed in a home (e.g., the home of the subject) or at a medical facility (e.g., doctor’s office, hospital, urgent care center, etc.).

[0211] In embodiments of the present invention relating to or involving detection or evaluation of NSCLC, the one or more proteins may be selected from Table 1. In some embodiments, the one or more proteins may be selected from Table LA. In certain embodiments, the one or more proteins are selected from Table l.B, Table l.C, Table l.D, Table l.E, or Table l.F. In particular embodiments, the one or more proteins comprise at least the proteins set forth in Table LG.

[0212] In embodiments of the present invention relating to or involving detection or evaluation of NSCLC and in which the subject is female, the one or more proteins may be selected from Table 2. In some embodiments, the one or more proteins are selected from Table 2.A. In certain embodiments, the one or more proteins are selected from Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F. In particular embodiments, the one or more proteins comprise at least the proteins set forth in Table 2.G.

[0213] In embodiments of the present invention relating to or involving detection or evaluation of NSCLC and in which the subject is male, the one or more proteins may be selected from Table 3. In some embodiments, the one or more proteins are selected from Table 3.A. In certain embodiments, the one or more proteins are selected from Table 3.B,Table 3.C, Table 3.D, Table 3.E, or Table 3.F. In particular embodiments, the one or more proteins comprise at least the proteins set forth in Table 3.G.

[0214] In embodiments of the present invention relating to or involving detection or evaluation of SCLC, the one or more proteins may be selected from Table 4. In some embodiments, the one or more proteins may be selected from Table 4.A. In certain embodiments, the one or more proteins are selected from Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F. In particular embodiments, the one or more proteins comprise at least the proteins set forth in Table 4.G.

[0215] In embodiments of the present invention relating to or involving detection or evaluation of SCLC and in which the subject is female, the one or more proteins may be selected from Table 5. In some embodiments, the one or more proteins are selected from Table 5.A. In certain embodiments, the one or more proteins are selected from Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F. In particular embodiments, the one or more proteins comprise at least the proteins set forth in Table 5.G.

[0216] In embodiments of the present invention relating to or involving detection or evaluation of SCLC and in which the subject is male, the one or more proteins may be selected from Table 6. In some embodiments, the one or more proteins are selected from Table 6.A. In certain embodiments, the one or more proteins are selected from Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F. In particular embodiments, the one or more proteins comprise at least the proteins set forth in Table 6.G.

[0217] In some embodiments of the present invention, for any of the proteins, the methods may comprise determining the concentration of two or more, or three or more, or four or more, or five or more, or six or more, or seven or more, or eight or more, or nine or more, or ten or more, or about 15 or more, or about 20 or more, or about 25 or more, or about 30 or more, or about 35 or more, or about 40 or more, or about 40 or more, or about 45 or more, or about 50 or more, or about 55 or more, or about 60 or more, or about 65 or more, or about 70 or more, or about 75 or more, or about 80 or more, or about 85 or more, or about 90 or more, or about 95 or more, or about 100 or more, or about 110 or more, or about 120 or more, or about 130 or more, or about 140 or more, or about 150 or more, or about 160 or more, proteins; including any number of proteins chosen from two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, or 161; and including any ranges thereof, for example, about two to 161 proteins, or about two to 160 proteins, or about two to 155 proteins, or about two to 150 proteins, or about two to 145 proteins, or about two to 140 proteins, or about two to 135 proteins, or about two to 130 proteins, or about two to 125 proteins, or about two to 120 proteins, or about two to 115 proteins, or about two to 110 proteins, or about two to 105 proteins, or about two to 100 proteins, or about two to 95 proteins, or about two to 90 proteins, or about two to 85 proteins, or about two to 80 proteins, or about two to 75 proteins, or about two to 70 proteins, or about two to 65 proteins, or about two to 60 proteins, or about two to 55 proteins, or about two to 50 proteins, or about two to 45 proteins, or about two to 40 proteins, or about two to 35 proteins, or about two to 30 proteins, or about two to 25 proteins, or about two to 20 proteins, or about two to 15 proteins, or about two to ten proteins, or about two to nine proteins, or about two to eight proteins, or about two to seven proteins, or about two to six proteins, or about two to five proteins, or about two to four proteins, or about two or three proteins, or about three to 161 proteins, or about three to 160 proteins, or about three to 155 proteins, or about three to 150 proteins, or about three to 145 proteins, or about three to 140 proteins, or about three to 135 proteins, or about three to 130 proteins, or about three to 125 proteins, or about three to 120 proteins, or about three to 115 proteins, or about three to 110 proteins, or about three to 105 proteins, or about three to 100 proteins, or about three to 95 proteins, or about three to 90 proteins, or about three to 85 proteins, or about three to 80 proteins, or about three to 75 proteins, or about three to 70 proteins, or about three to 65 proteins, or about three to 60 proteins, or about three to 55 proteins, or about three to 50 proteins, or about three to 45 proteins, or about three to 40 proteins, or about three to 35 proteins, or about three to 30 proteins, or about three to 25 proteins, or about three to 20 proteins, or about three to 15 proteins, or about three to ten proteins, or about three to nine proteins, or about three to eight proteins, or about three to seven proteins, or about three to six proteins, or about three to five proteins, or about three or four proteins,or about five to 161 proteins, or about five to 160 proteins, or about five to 155 proteins, or about five to 150 proteins, or about five to 145 proteins, or about five to 140 proteins, or about five to 135 proteins, or about five to 130 proteins, or about five to 125 proteins, or about five to 120 proteins, or about five to 115 proteins, or about five to 110 proteins, or about five to 105 proteins, or about five to 100 proteins, or about five to 95 proteins, or about five to 90 proteins, or about five to 85 proteins, or about five to 80 proteins, or about five to 75 proteins, or about five to 70 proteins, or about five to 65 proteins, or about five to 60 proteins, or about five to 55 proteins, or about five to 50 proteins, or about five to 45 proteins, or about five to 40 proteins, or about five to 35 proteins, or about five to 30 proteins, or about five to 25 proteins, or about five to 20 proteins, or about five to 15 proteins, or about five to ten proteins, or about five to nine proteins, or about five to eight proteins, or about five to seven proteins, or about five or six proteins, or about ten to 161 proteins, or about ten to 160 proteins, or about ten to 155 proteins, or ten three to 150 proteins, or about ten to 145 proteins, or about ten to 140 proteins, or about ten to 135 proteins, or about ten to 130 proteins, or about ten to 125 proteins, or about ten to 120 proteins, or about ten to 115 proteins, or about ten to 110 proteins, or about ten to 105 proteins, or about ten to 100 proteins, or about ten to 95 proteins, or about ten to 90 proteins, or about ten to 85 proteins, or about ten to 80 proteins, or about ten to 75 proteins, or about ten to 70 proteins, or about ten to 65 proteins, or about ten to 60 proteins, or about ten to 55 proteins, or about ten to 50 proteins, or about ten to 45 proteins, or about ten to 40 proteins, or about ten to 35 proteins, or about ten to 30 proteins, or about ten to 25 proteins, or about ten to 20 proteins, or about ten to 15 proteins, or about 15 to 161 proteins, or about 15 to 160 proteins, or about 15 to 155 proteins, or about 15 to 150 proteins, or about 15 to 145 proteins, or about 15 to 140 proteins, or about 15 to 135 proteins, or about 15 to 130 proteins, or about 15 to 125 proteins, or about 15 to 120 proteins, or about 15 to 115 proteins, or about 15 to 110 proteins, or about 15 to 105 proteins, or about 15 to 100 proteins, or about 15 to 95 proteins, or about 15 to 90 proteins, or about 15 to 85 proteins, or about 15 to 80 proteins, or about 15 to 75 proteins, or about 15 to 70 proteins, or about 15 to 65 proteins, or about 15 to 60 proteins, or about 15 to 55 proteins, or about 15 to 50 proteins, or about 15 to 45 proteins, or about 15 to 40 proteins, or about 15 to 35 proteins, or about 15 to 30 proteins, or about 15 to 25 proteins, or about 15 to 20 proteins, or about 20 to 161 proteins, or about 20 to 160 proteins, or about 20 to 155 proteins, or about 20 to 150 proteins, or about 20 to 145 proteins, or about 20 to 140 proteins,or about 20 to 135 proteins, or about 20 to 130 proteins, or about 20 to 125 proteins, or about 20 to 120 proteins, or about 20 to 115 proteins, or about 20 to 110 proteins, or about 20 to 105 proteins, or about 20 to 100 proteins, or about 20 to 95 proteins, or about 20 to 90 proteins, or about 20 to 85 proteins, or about 20 to 80 proteins, or about 20 to 75 proteins, or about 20 to 70 proteins, or about 20 to 65 proteins, or about 20 to 60 proteins, or about 20 to 55 proteins, or about 20 to 50 proteins, or about 20 to 45 proteins, or about 20 to 40 proteins, or about 20 to 35 proteins, or about 20 to 30 proteins, or about 20 to 25 proteins, or about 25 to 161 proteins, or about 25 to 160 proteins, or about 25 to 155 proteins, or about 25 to 150 proteins, or about 25 to 145 proteins, or about 25 to 140 proteins, or about 25 to 135 proteins, or about 25 to 130 proteins, or about 25 to 125 proteins, or about 25 to 120 proteins, or about 25 to 115 proteins, or about 25 to 110 proteins, or about 25 to 105 proteins, or about 25 to 100 proteins, or about 25 to 95 proteins, or about 25 to 90 proteins, or about 25 to 85 proteins, or about 25 to 80 proteins, or about 25 to 75 proteins, or about 25 to 70 proteins, or about 25 to 65 proteins, or about 25 to 60 proteins, or about 25 to 55 proteins, or about 25 to 50 proteins, or about 25 to 45 proteins, or about 25 to 40 proteins, or about 25 to 30 proteins, or about 30 to 161 proteins, or about 30 to 160 proteins, or about 30 to 155 proteins, or about 30 to 150 proteins, or about 30 to 145 proteins, or about 30 to 140 proteins, or about 30 to 135 proteins, or about 30 to 130 proteins, or about 30 to 125 proteins, or about 30 to 120 proteins, or about 30 to 115 proteins, or about 30 to 110 proteins, or about 30 to 105 proteins, or about 30 to 100 proteins, or about 30 to 95 proteins, or about 30 to 90 proteins, or about 30 to 85 proteins, or about 30 to 80 proteins, or about 30 to 75 proteins, or about 30 to 70 proteins, or about 30 to 65 proteins, or about 30 to 60 proteins, or about 30 to 55 proteins, or about 30 to 50 proteins, or about 30 to 45 proteins, or about 30 to 40 proteins, or about 30 to 35 proteins, or about 35 to 161 proteins, or about 35 to 160 proteins, or about 35 to 155 proteins, or about 35 to 150 proteins, or about 35 to 145 proteins, or about 35 to 140 proteins, or about 35 to 135 proteins, or about 35 to 130 proteins, or about 35 to 125 proteins, or about 35 to 120 proteins, or about 35 to 115 proteins, or about 35 to 110 proteins, or about 35 to 105 proteins, or about 35 to 100 proteins, or about 35 to 95 proteins, or about 35 to 90 proteins, or about 35 to 85 proteins, or about 35 to 80 proteins, or about 35 to 75 proteins, or about 35 to 70 proteins, or about 35 to 65 proteins, or about 35 to 60 proteins, or about 35 to 55 proteins, or about 35 to 50 proteins, or about 35 to 45 proteins, or about 35 to 40 proteins, or about 40 to 161 proteins, or about 40 to 160 proteins, or about 40 to 155 proteins, or about40 to 150 proteins, or about 40 to 145 proteins, or about 40 to 140 proteins, or about 40 to 135 proteins, or about 40 to 130 proteins, or about 40 to 125 proteins, or about 40 to 120 proteins, or about 40 to 115 proteins, or about 40 to 110 proteins, or about 40 to 105 proteins, or about 40 to 100 proteins, or about 40 to 95 proteins, or about 40 to 90 proteins, or about 40 to 85 proteins, or about 40 to 80 proteins, or about 40 to 75 proteins, or about 40 to 70 proteins, or about 40 to 65 proteins, or about 40 to 60 proteins, or about 40 to 55 proteins, or about 40 to 50 proteins, or about 40 to 45 proteins, or about 45 to 161 proteins, or about 45 to 160 proteins, or about 45 to 155 proteins, or about 45 to 150 proteins, or about 45 to 145 proteins, or about 45 to 140 proteins, or about 45 to 135 proteins, or about 45 to 130 proteins, or about 45 to 125 proteins, or about 45 to 120 proteins, or about 45 to 115 proteins, or about 45 to 110 proteins, or about 45 to 105 proteins, or about 45 to 100 proteins, or about 45 to 95 proteins, or about 45 to 90 proteins, or about 45 to 85 proteins, or about 45 to 80 proteins, or about 45 to 75 proteins, or about 45 to 70 proteins, or about 45 to 65 proteins, or about 45 to 60 proteins, or about 45 to 55 proteins, or about 45 to 50 proteins, or about 50 to 161 proteins, or about 50 to 160 proteins, or about 50 to 155 proteins, or about 50 to 150 proteins, or about 50 to 145 proteins, or about 50 to 140 proteins, or about 50 to 135 proteins, or about 50 to 130 proteins, or about 50 to 125 proteins, or about 50 to 120 proteins, or about 50 to 115 proteins, or about 50 to 110 proteins, or about 50 to 105 proteins, or about 50 to 100 proteins, or about 50 to 95 proteins, or about 50 to 90 proteins, or about 50 to 85 proteins, or about 50 to 80 proteins, or about 50 to 75 proteins, or about 50 to 70 proteins, or about 50 to 65 proteins, or about 50 to 60 proteins, or about 50 to 55 proteins, or about 55 to 161 proteins, or about 55 to 160 proteins, or about 55 to 155 proteins, or about 55 to 150 proteins, or about 55 to 145 proteins, or about 55 to 140 proteins, or about 55 to 135 proteins, or about 55 to 130 proteins, or about 55 to 125 proteins, or about 55 to 120 proteins, or about 55 to 115 proteins, or about 55 to 110 proteins, or about 55 to 105 proteins, or about 55 to 100 proteins, or about 55 to 95 proteins, or about 55 to 90 proteins, or about 55 to 85 proteins, or about 55 to 80 proteins, or about 55 to 75 proteins, or about 55 to 70 proteins, or about 55 to 65 proteins, or about 55 to 60 proteins, or about 60 to 161 proteins, or about 60 to 160 proteins, or about 60 to 155 proteins, or about 60 to 150 proteins, or about 60 to 145 proteins, or about 60 to 140 proteins, or about 60 to 135 proteins, or about 60 to 130 proteins, or about 60 to 125 proteins, or about 60 to 120 proteins, or about 60 to 115 proteins, or about 60 to 110 proteins, or about 60 to 105 proteins, or about 60 to 100 proteins, or about 60 to 95proteins, or about 60 to 90 proteins, or about 60 to 85 proteins, or about 60 to 80 proteins, or about 60 to 75 proteins, or about 60 to 70 proteins, or about 60 to 65 proteins, or about 65 to 161 proteins, or about 65 to 160 proteins, or about 65 to 155 proteins, or about 65 to 150 proteins, or about 65 to 145 proteins, or about 65 to 140 proteins, or about 65 to 135 proteins, or about 65 to 130 proteins, or about 65 to 125 proteins, or about 65 to 120 proteins, or about 65 to 115 proteins, or about 65 to 110 proteins, or about 65 to 105 proteins, or about 65 to 100 proteins, or about 65 to 95 proteins, or about 65 to 90 proteins, or about 65 to 85 proteins, or about 65 to 80 proteins, or about 65 to 75 proteins, or about 65 to 70 proteins, or about 70 to 161 proteins, or about 70 to 160 proteins, or about 70 to 155 proteins, or about 70 to 150 proteins, or about 70 to 145 proteins, or about 70 to 140 proteins, or about 70 to 135 proteins, or about 70 to 130 proteins, or about 70 to 125 proteins, or about 70 to 120 proteins, or about 70 to 115 proteins, or about 70 to 110 proteins, or about 70 to 105 proteins, or about 70 to 100 proteins, or about 70 to 95 proteins, or about 70 to 90 proteins, or about 70 to 85 proteins, or about 70 to 80 proteins, or about 70 to 75 proteins, or about 75 to 161 proteins, or about 75 to 160 proteins, or about 75 to 155 proteins, or about 75 to 150 proteins, or about 75 to 145 proteins, or about 75 to 140 proteins, or about 75 to 135 proteins, or about 75 to 130 proteins, or about 75 to 125 proteins, or about 75 to 120 proteins, or about 75 to 115 proteins, or about 75 to 110 proteins, or about 75 to 105 proteins, or about 75 to 100 proteins, or about 75 to 95 proteins, or about 75 to 90 proteins, or about 75 to 85 proteins, or about 75 to 80 proteins, or about 80 to 161 proteins, or about 80 to 160 proteins, or about 80 to 155 proteins, or about 80 to 150 proteins, or about 80 to 145 proteins, or about 80 to 140 proteins, or about 80 to 135 proteins, or about 80 to 130 proteins, or about 80 to 125 proteins, or about 80 to 120 proteins, or about 80 to 115 proteins, or about 80 to 110 proteins, or about 80 to 105 proteins, or about 80 to 100 proteins, or about 80 to 95 proteins, or about 80 to 90 proteins, or about 80 to 85 proteins, or about 85 to 161 proteins, or about 85 to 160 proteins, or about 85 to 155 proteins, or about 85 to 150 proteins, or about 85 to 145 proteins, or about 85 to 140 proteins, or about 85 to 135 proteins, or about 85 to 130 proteins, or about 85 to 125 proteins, or about 85 to 120 proteins, or about 85 to 115 proteins, or about 85 to 110 proteins, or about 85 to 105 proteins, or about 85 to 100 proteins, or about 85 to 95 proteins, or about 85 to 90 proteins, or about 90 to 161 proteins, or about 90 to 160 proteins, or about 90 to 155 proteins, or about 90 to 150 proteins, or about 90 to 145 proteins, or about 90 to 140 proteins, or about 90 to 135 proteins, or about 90 to 130 proteins, or about 90 to 125 proteins, or about 90 to120 proteins, or about 90 to 115 proteins, or about 90 to 110 proteins, or about 90 to 105 proteins, or about 90 to 100 proteins, or about 90 to 95 proteins, or about 95 to 161 proteins, or about 95 to 160 proteins, or about 95 to 155 proteins, or about 95 to 150 proteins, or about 95 to 145 proteins, or about 95 to 140 proteins, or about 95 to 135 proteins, or about 95 to 130 proteins, or about 95 to 125 proteins, or about 95 to 120 proteins, or about 95 to 115 proteins, or about 95 to 110 proteins, or about 95 to 105 proteins, or about 95 to 100 proteins, or about 100 to 161 proteins, or about 100 to 160 proteins, or about 100 to 155 proteins, or about 100 to 150 proteins, or about 100 to 145 proteins, or about 100 to 140 proteins, or about 100 to 135 proteins, or about 100 to 130 proteins, or about 100 to 125 proteins, or about 100 to 120 proteins, or about 100 to 115 proteins, or about 100 to 110 proteins, or about 100 to 105 proteins, or about 105 to 161 proteins, or about 105 to 160 proteins, or about 105 to 155 proteins, or about 105 to 150 proteins, or about 105 to 145 proteins, or about 105 to 140 proteins, or about 105 to 135 proteins, or about 105 to 130 proteins, or about 105 to 125 proteins, or about 105 to 120 proteins, or about 105 to 115 proteins, or about 105 to 110 proteins, or about 110 to 161 proteins, or about 110 to 160 proteins, or about 110 to 155 proteins, or about 110 to 150 proteins, or about 110 to 145 proteins, or about 110 to 140 proteins, or about 110 to 135 proteins, or about 110 to 130 proteins, or about 110 to 125 proteins, or about 110 to 120 proteins, or about 110 to 115 proteins, or about 115 to 161 proteins, or about 115 to 160 proteins, or about 115 to 155 proteins, or about 115 to 150 proteins, or about 115 to 145 proteins, or about 115 to 140 proteins, or about 115 to 135 proteins, or about 115 to 130 proteins, or about 115 to 125 proteins, or about 115 to 120 proteins, or about 120 to 161 proteins, or about 120 to 160 proteins, or about 120 to 155 proteins, or about 120 to 150 proteins, or about 120 to 145 proteins, or about 120 to 140 proteins, or about 120 to 135 proteins, or about 120 to 130 proteins, or about 120 to 125 proteins, or about 125 to 161 proteins, or about 125 to 160 proteins, or about 125 to 155 proteins, or about 125 to 150 proteins, or about 125 to 145 proteins, or about 125 to 140 proteins, or about 125 to 135 proteins, or about 125 to 130 proteins, or about 130 to 161 proteins, or about 130 to 160 proteins, or about 130 to 155 proteins, or about 130 to 150 proteins, or about 130 to 145 proteins, or about 130 to 140 proteins, or about 130 to 135 proteins, or about 135 to 161 proteins, or about 135 to 160 proteins, or about 135 to 155 proteins, or about 135 to 150 proteins, or about 135 to 145 proteins, or about 135 to 140 proteins, or about 140 to 161 proteins, or about 140 to 160 proteins, orabout 140 to 155 proteins, or about 140 to 150 proteins, or about 140 to 145 proteins, or about 145 to 161 proteins, or about 145 to 160 proteins, or about 145 to 150 proteins, or about 150 to 161 proteins, or about 150 to 160 proteins, or about 150 to 155 proteins, or about 155 to 161 proteins, or about 155 to 160 proteins, or about 160 to 161 proteins.

[0218] In some embodiments, the methods may comprise determining the concentration of each protein of Table 1 or Table 2 or Table 3 or Table 4 or Table 5 or Table 6 or Table 7 or Table 8 or Table 9. In some embodiments, the methods may comprise determining the concentration of each protein of Table l.A or Table l.B or Table l.C or Table l.D or Table l.E or Table l.F or Table l.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 2.A or Table 2.B or Table 2.C or Table 2.D or Table 2.E or Table 2.F or Table 2.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 3.A or Table 3.B or Table 3.C or Table 3.D or Table 3.E or Table 3.F or Table 3.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 4.A or Table 4.B or Table 4.C or Table 4.D or Table 4.E or Table 4.F or Table 4.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 5.A or Table 5.B or Table 5.C or Table 5.D or Table 5.E or Table 5.F or Table 5.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 6.A or Table 6.B or Table 6.C or Table 6.D or Table 6.E or Table 6.F or Table 6.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 7.A or Table 7.B or Table 7.C or Table 7.D or Table 7.E or Table 7.F or Table 7.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 8.A or Table 8.B or Table 8.C or Table 8.D or Table 8.E or Table 8.F or Table 8.G. In certain embodiments, the methods may comprise determining the concentration of each protein of Table 9.A or Table 9.B or Table 9.C or Table 9.D or Table 9.E or Table 9.F or Table 9.G.

[0219] In some embodiments, the number of proteins for which the concentration is determined may be sufficient to achieve an AUC of a ROC curve of at least about 0.6. In certain embodiments, the number of proteins for which the concentration is determined may be sufficient to achieve an AUC of a ROC curve of at least about 0.7, or at least about 0.8, or at least about 0.9.

[0220] In embodiments of the invention, the cancer is early-stage. In some embodiments, the cancer is stage I. In some embodiments, the cancer is stage II.

[0221] In some embodiments, the cancer is stage III. In some embodiments, the cancer is stage IV. In some embodiments, the cancer is stage V.

[0222] The treatment for NSCLC or lung cancer that may be NSCLC or SCLC administered to the subjects according to the methods described herein may be treatments known in the art. Examples of such treatments include, but are not limited to, surgery, radiation therapy, chemotherapy, immunotherapy, laser therapy, photodynamic therapy, cryosurgery, electrocautery, and any combination thereof. Examples of surgery may include, but are not limited, to wedge / segmental resection, which removes a tumor and some of the normal tissue around it); lobectomy, which removes a whole lobe of the lung; pneumonectomy, which removes one whole lung; and sleeve resection, which removes part of the bronchus. Examples of radiation therapy include, but are not limited to, external radiation therapy such as stereotactic body radiation therapy or stereotactic radiosurgery; and internal radiation therapy. Examples of chemotherapy include, but are not limited to, monoclonal antibodies such as bevacizumab, ramucirumab, cetuximab, and necitumumab; tyrosine kinase inhibitors, such as erlotinib, gefitinib, afatinib, osimertinib, dacomitinib, amivantamab, dabrafenib, trametinib, crizotinib, entrectinib, ceritinib, alectinib, brigatinib, lorlatinib, larotrectinib, entrectinib, selpercatinib, pralsetinib, tepotinib, and capmatinib; mammalian target of rapamycin (mTOR) inhibitors, such as everolimus; KRAS G12C inhibitors, such as sotorasib and adagrasib; and any combination thereof. Examples of immunotherapy include, but are not limited to, programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors such as pembrolizumab, nivolumab, cemiplimab, atezolizumab, and durvalumab; cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors such as tremelimumab; and any combination thereof.

[0223] The treatment for SCLC or lung cancer that may be NSCLC or SCLC administered to the subjects according to the methods described herein may be treatments known in the art. Examples of such treatments include, but are not limited to, surgery, radiation therapy, chemotherapy, and immunotherapy. Examples of surgery may include, but are not limited, to wedge / segmental resection, lobectomy, pneumonectomy, and sleeve resection. Examples of radiation therapy include, but are not limited to, three-dimensionalconformal radiation therapy, intensity modulated radiation therapy, four-dimensional conformal radiation therapy, stereotactic body radiation therapy, and any combination thereof. Examples of chemotherapy include, but are not limited to, cisplatin, cisplatin with etoposide, carboplatin, carboplatin with etoposide, topotecan, lurbinectedin, docetaxel, paclitaxel, gemcitabine, irinotecan, temozolomide, vinorelbine, and any combination thereof. Examples of immunotherapy include, but are not limited to, PD-L1 inhibitors such as atezolizumab and durvalumab, bispecific T-cell engagers such as tarlatamab, and any combination thereof.

[0224] In certain embodiments, a cancer patient subjected to a method of the invention is successfully treated if the patient’s survival is longer than the median survival of patients having NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC.Survival can be overall survival, z.e., length of time a patient lives, or progression-free survival, z.e., length of time a patient is treated without progression of the disease. Survival can be measured from the date of diagnosis or from the date that treatment commences. Overall survival, median overall survival, progression-free survival, and median progression- free survival can be determined by methods known in the art and / or by those described herein.

[0225] In certain embodiments a patient with NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC, subjected to a method of the invention is successfully treated if the patient has an improved response to the anti-cancer therapy compared with a patient having NSCLC, SCLC, or lung cancer that may be either NSCLC or SCLC who has not been subjected to a method of the invention. For example, treatment would be successful in a subject treated by the methods of the invention if the subject has an improved response compared to the median response of patients who have not been treated by the methods of the invention. Response to anti-cancer treatment can be measured by known methods appropriate to the cancer type, for instance, using Response Evaluation Criteria in Solid Tumors (RECIST). Patients evaluated using RECIST can have a complete response (CR), a partial response (PR), stable disease (SD), or progressive disease (PD). An improved response can also be assessed by other criteria, for example, duration of response, reduction in tumor volume, minimum residual disease (MRD), and the like.Protein Concentration Measurement and Application of Classifiers

[0226] The concentration of proteins in the sample may be measured using protein quantitation techniques known in the art. Such techniques include, but are not limited to, enzyme-linked immunosorbent assays, chemiluminescence immunoassays, immunohistochemistry, liquid-bead immunoassays, mass spectrometry, aptamer-based assays, reverse phase protein arrays, proximity extension assay (PEA), and a combination thereof.

[0227] In the methods described herein, the concentration of the two or more proteins are used and combined with mathematical, statistical, and machine-learning methods to create secondary features. One or more proteins with and without secondary features and baseline features, including age, sex, race and ethnicity, past medical history, family history, patient’s lab values, comorbidities, and concomitant medications, are used in one or more predictive models to calculate a score.

[0228] Machine learning and statistical analyses techniques used to generate features and the final score for the cancer are included but not limited to the following concepts and methods: Supervised learning concepts may include AODE; Artificial neural network, such as B ackpropagation, Auto encoders, Hopfield networks, Boltzmann machines, Restricted Boltzmann Machines, and Spiking neural networks; Bayesian statistics, such as Bayesian network and Bayesian knowledge base; Case-based reasoning; Gaussian process regression; Gene expression programming; Group method of data handling (GMDH); Inductive logic programming; Instance-based learning; Lazy learning; Learning Automata; Learning Vector Quantization; Logistic Model Tree; Minimum message length (decision trees, decision graphs, etc.), such as Nearest Neighbor Algorithm and Analogical modeling; Probably approximately correct learning (PAC ) learning; Ripple down rules, a knowledge acquisition methodology; Symbolic machine learning algorithms; Support vector machines; Random Forests; Ensembles of classifiers, such as Bootstrap aggregating (bagging) and Boosting (meta -algorithm ); Ordinal classification; Information fuzzy networks (IFN); Conditional Random Field; ANOVA; Linear classifiers, such as Fisher’s linear discriminant, Linear regression, Logistic regression, Multinomial logistic regression, I Bayes classifier, Perceptron, Support vector machines; Quadratic classifiers; k -nearest neighbor; Boosting; Decision trees, such as C4.5, Random forests, ID3, CART, SLIQ SPRINT; Bayesiannetworks, sucINaive Bayes; and Hidden Markov models . Unsupervised learning concepts may include; Expectation -maximization algorithm; Vector Quantization; Generative topographic map; Information bottleneck method; Artificial neural network, such as Self - organizing map; Association rule learning, such as Apriori algorithm, Eclat algorithm, and FP growth algorithm; Hierarchical clusterings such as Single linkage clustering and Conceptual clustering; Cluster analysis, such as K -means algorithm, Fuzzy clustering, DBSCAN, and OPTICS algorithm; and Outlier Detection, such as Local Outlier Factor. Semi-supervised learning concepts may include; Generative models; Low -density separation; Graph-based methods, and Co -training. Reinforcement learning concepts may include Temporal difference learning; Q -learning, Learning Automata, and SARSA. Deep learning concepts may include Deep belief networks; Deep Boltzmann machines; Deep Convolutional neural networks; Deep Recurrent neural networks; and Hierarchical temporal memory.

[0229] For concentrations obtained from detection proteins, one or more features are fed into one or more computation models. The classifiers are used to calculate a score for the patient. The scores of different classifiers are combined to identify the patient as having the specific cancer or not. The computational model may use one or more proteins or secondary features with and without baseline features that could generate a (ROC curve greater than or equal to 0.6. This step determines if the sample indicates the presence of the cancer.

[0230] Protein concentrations and / or secondary features are fed into one or more predictive models. The features could be similar or different from what was used in determining cancer status. The classifiers are used to calculate a score for the patient for NSCLC. The predictive models use the proteins or derived secondary features that could generate a ROC curve greater than or equal to 0.6.

[0231] Generally, machine learning algorithms are used to construct models that accurately assign class labels to examples based on the input features that describe the example.

[0232] Embodiments of the present disclosure can be further defined by reference to the following non-limiting examples. It will be apparent to those skilled in the art that many modifications, both to materials and methods, can be practiced without departing from the scope of the present disclosure.Kit

[0233] An aspect of the present invention relates to a kit for use in detecting one or more proteins of Table 1 (such as one or more proteins of Table l.A, Table 1.B, Table l.C, Table l.D, Table l.E, or Table l.F, or at least each protein of Table l.G), or one or more proteins of Table 2 (such as one or more proteins of Table 2.A, Table 2.B, Table 2.C, Table2.D, Table 2.E, or Table 2.F, or at least each protein of Table 2.G), or one or more proteins of Table 3 (such as one or more proteins of Table 3.A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F, or at least each protein of Table 3.G), or one or more proteins of Table 4 (such as one or more proteins of Table 4.A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F, or at least each protein of Table 4.G), or one or more proteins of Table 5 (such as one or more proteins of Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F, or at least each protein of Table 5.G), or one or more proteins of Table 6 (such as one or more proteins of Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F, or at least each protein of Table 6.G), or one or more proteins of Table 7 (such as one or more proteins of Table73.A, Table 7.B, Table 7.C, Table 7.D, Table 7.E, or Table 7.F, or at least each protein of Table 7.G) , or one or more proteins of Table 8 (such as one or more proteins of Table 8.A, Table 8.B, Table 8.C, Table 8.D, Table 8.E, or Table 8.F, or at least each protein of Table 8.G), or one or more proteins of Table 9 (such as one or more proteins of Table 9.A, Table 9.B, Table 9.C, Table 9.D, Table 9.E, or Table 9.F, or at least each protein of Table 9.G), which can be used to perform the methods described herein. The kit may comprise one or more components that can be used to perform assays such as enzyme-linked immunosorbent assays, chemiluminescence immunoassays, immunohistochemistry, liquid-bead immunoassays, mass spectrometry, aptamer-based assays, reverse phase protein arrays, PEA, or a combination thereof. Such components include, but are not limited to, antibodies or antigen binding fragments thereof that bind one or more proteins of Table 1 (such as one or more proteins of Table 1.A, Table l.B, Table l.C, Table l.D, Table l.E, or Table l.F, or at least each protein of Table l.G), or one or more proteins of Table 2 (such as one or more proteins of Table 2. A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F, or at least each protein of Table 2.G), or one or more proteins of Table 3 (such as one or more proteins of Table 3. A, Table 3.B, Table3.C, Table 3.D, Table 3.E, or Table 3.F, or at least each protein of Table 3.G), or one or more proteins of Table 4 (such as one or more proteins of Table 4.A, Table 4.B, Table 4.C,Table 4.D, Table 4.E, or Table 4.F, or at least each protein of Table 4.G), or one or more proteins of Table 5 (such as one or more proteins of Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F, or at least each protein of Table 5.G), or one or more proteins of Table 6 (such as one or more proteins of Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F, or at least each protein of Table 6.G), or one or more proteins of Table 7 (such as one or more proteins of Table73.A, Table 7.B, Table 7.C, Table 7.D, Table 7.E, or Table 7.F, or at least each protein of Table 7.G) , or one or more proteins of Table 8 (such as one or more proteins of Table 8.A, Table 8.B, Table 8.C, Table 8.D, Table 8.E, or Table 8.F, or at least each protein of Table 8.G), or one or more proteins of Table 9 (such as one or more proteins of Table 9.A, Table 9.B, Table 9.C, Table 9.D, Table 9.E, or Table 9.F, or at least each protein of Table 9.G).

[0234] In some embodiments, the kit comprises antibodies or antigen binding fragments thereof that bind two or more, or three or more, or four or more, or five or more, or six or more, or seven or more, or eight or more, or nine or more, or ten or more, or about 15 or more, or about 20 or more, or about 25 or more, or about 30 or more, or about 35 or more, or about 40 or more, or about 40 or more, or about 45 or more, or about 50 or more, or about 55 or more, or about 60 or more, or about 65 or more, or about 70 or more, or about 75 or more, or about 80 or more, or about 85 or more, or about 90 or more, or about 95 or more, or about 100 or more, or about 110 or more, or about 120 or more, or about 130 or more, or about 140 or more, or about 150 or more, or about 160 or more, proteins; including any number of proteins chosen from two, three, four, five, six, seven, eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109,110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, or 161; and including any ranges thereof, for example, about two to 161 proteins, or about two to 160 proteins, or about two to 155 proteins, or about two to 150 proteins, or about two to 145 proteins, or about two to 140 proteins, or about two to 135 proteins, or about two to 130 proteins, or about two to 125 proteins, or about two to 120 proteins, or about two to 115proteins, or about two to 110 proteins, or about two to 105 proteins, or about two to 100 proteins, or about two to 95 proteins, or about two to 90 proteins, or about two to 85 proteins, or about two to 80 proteins, or about two to 75 proteins, or about two to 70 proteins, or about two to 65 proteins, or about two to 60 proteins, or about two to 55 proteins, or about two to 50 proteins, or about two to 45 proteins, or about two to 40 proteins, or about two to 35 proteins, or about two to 30 proteins, or about two to 25 proteins, or about two to 20 proteins, or about two to 15 proteins, or about two to ten proteins, or about two to nine proteins, or about two to eight proteins, or about two to seven proteins, or about two to six proteins, or about two to five proteins, or about two to four proteins, or about two or three proteins, or about three to 161 proteins, or about three to 160 proteins, or about three to 155 proteins, or about three to 150 proteins, or about three to 145 proteins, or about three to 140 proteins, or about three to 135 proteins, or about three to 130 proteins, or about three to 125 proteins, or about three to 120 proteins, or about three to 115 proteins, or about three to 110 proteins, or about three to 105 proteins, or about three to 100 proteins, or about three to 95 proteins, or about three to 90 proteins, or about three to 85 proteins, or about three to 80 proteins, or about three to 75 proteins, or about three to 70 proteins, or about three to 65 proteins, or about three to 60 proteins, or about three to 55 proteins, or about three to 50 proteins, or about three to 45 proteins, or about three to 40 proteins, or about three to 35 proteins, or about three to 30 proteins, or about three to 25 proteins, or about three to 20 proteins, or about three to 15 proteins, or about three to ten proteins, or about three to nine proteins, or about three to eight proteins, or about three to seven proteins, or about three to six proteins, or about three to five proteins, or about three or four proteins, or about five to 161 proteins, or about five to 160 proteins, or about five to 155 proteins, or about five to 150 proteins, or about five to 145 proteins, or about five to 140 proteins, or about five to 135 proteins, or about five to 130 proteins, or about five to 125 proteins, or about five to 120 proteins, or about five to 115 proteins, or about five to 110 proteins, or about five to 105 proteins, or about five to 100 proteins, or about five to 95 proteins, or about five to 90 proteins, or about five to 85 proteins, or about five to 80 proteins, or about five to 75 proteins, or about five to 70 proteins, or about five to 65 proteins, or about five to 60 proteins, or about five to 55 proteins, or about five to 50 proteins, or about five to 45 proteins, or about five to 40 proteins, or about five to 35 proteins, or about five to 30 proteins, or about five to 25 proteins, or about five to 20 proteins, or about five to 15 proteins, or about five to ten proteins, or about five tonine proteins, or about five to eight proteins, or about five to seven proteins, or about five or six proteins, or about ten to 161 proteins, or about ten to 160 proteins, or about ten to 155 proteins, or ten three to 150 proteins, or about ten to 145 proteins, or about ten to 140 proteins, or about ten to 135 proteins, or about ten to 130 proteins, or about ten to 125 proteins, or about ten to 120 proteins, or about ten to 115 proteins, or about ten to 110 proteins, or about ten to 105 proteins, or about ten to 100 proteins, or about ten to 95 proteins, or about ten to 90 proteins, or about ten to 85 proteins, or about ten to 80 proteins, or about ten to 75 proteins, or about ten to 70 proteins, or about ten to 65 proteins, or about ten to 60 proteins, or about ten to 55 proteins, or about ten to 50 proteins, or about ten to 45 proteins, or about ten to 40 proteins, or about ten to 35 proteins, or about ten to 30 proteins, or about ten to 25 proteins, or about ten to 20 proteins, or about ten to 15 proteins, or about 15 to 161 proteins, or about 15 to 160 proteins, or about 15 to 155 proteins, or about 15 to 150 proteins, or about 15 to 145 proteins, or about 15 to 140 proteins, or about 15 to 135 proteins, or about 15 to 130 proteins, or about 15 to 125 proteins, or about 15 to 120 proteins, or about 15 to 115 proteins, or about 15 to 110 proteins, or about 15 to 105 proteins, or about 15 to 100 proteins, or about 15 to 95 proteins, or about 15 to 90 proteins, or about 15 to 85 proteins, or about 15 to 80 proteins, or about 15 to 75 proteins, or about 15 to 70 proteins, or about 15 to 65 proteins, or about 15 to 60 proteins, or about 15 to 55 proteins, or about 15 to 50 proteins, or about 15 to 45 proteins, or about 15 to 40 proteins, or about 15 to 35 proteins, or about 15 to 30 proteins, or about 15 to 25 proteins, or about 15 to 20 proteins, or about 20 to 161 proteins, or about 20 to 160 proteins, or about 20 to 155 proteins, or about 20 to 150 proteins, or about 20 to 145 proteins, or about 20 to 140 proteins, or about 20 to 135 proteins, or about 20 to 130 proteins, or about 20 to 125 proteins, or about 20 to 120 proteins, or about 20 to 115 proteins, or about 20 to 110 proteins, or about 20 to 105 proteins, or about 20 to 100 proteins, or about 20 to 95 proteins, or about 20 to 90 proteins, or about 20 to 85 proteins, or about 20 to 80 proteins, or about 20 to 75 proteins, or about 20 to 70 proteins, or about 20 to 65 proteins, or about 20 to 60 proteins, or about 20 to 55 proteins, or about 20 to 50 proteins, or about 20 to 45 proteins, or about 20 to 40 proteins, or about 20 to 35 proteins, or about 20 to 30 proteins, or about 20 to 25 proteins, or about 25 to 161 proteins, or about 25 to 160 proteins, or about 25 to 155 proteins, or about 25 to 150 proteins, or about 25 to 145 proteins, or about 25 to 140 proteins, or about 25 to 135 proteins, or about 25 to 130 proteins, or about 25 to 125 proteins, or about 25 to 120 proteins, or about 25 to 115 proteins, or about 25 to110 proteins, or about 25 to 105 proteins, or about 25 to 100 proteins, or about 25 to 95 proteins, or about 25 to 90 proteins, or about 25 to 85 proteins, or about 25 to 80 proteins, or about 25 to 75 proteins, or about 25 to 70 proteins, or about 25 to 65 proteins, or about 25 to 60 proteins, or about 25 to 55 proteins, or about 25 to 50 proteins, or about 25 to 45 proteins, or about 25 to 40 proteins, or about 25 to 30 proteins, or about 30 to 161 proteins, or about 30 to 160 proteins, or about 30 to 155 proteins, or about 30 to 150 proteins, or about 30 to 145 proteins, or about 30 to 140 proteins, or about 30 to 135 proteins, or about 30 to 130 proteins, or about 30 to 125 proteins, or about 30 to 120 proteins, or about 30 to 115 proteins, or about 30 to 110 proteins, or about 30 to 105 proteins, or about 30 to 100 proteins, or about 30 to 95 proteins, or about 30 to 90 proteins, or about 30 to 85 proteins, or about 30 to 80 proteins, or about 30 to 75 proteins, or about 30 to 70 proteins, or about 30 to 65 proteins, or about 30 to 60 proteins, or about 30 to 55 proteins, or about 30 to 50 proteins, or about 30 to 45 proteins, or about 30 to 40 proteins, or about 30 to 35 proteins, or about 35 to 161 proteins, or about 35 to 160 proteins, or about 35 to 155 proteins, or about 35 to 150 proteins, or about 35 to 145 proteins, or about 35 to 140 proteins, or about 35 to 135 proteins, or about 35 to 130 proteins, or about 35 to 125 proteins, or about 35 to 120 proteins, or about 35 to 115 proteins, or about 35 to 110 proteins, or about 35 to 105 proteins, or about 35 to 100 proteins, or about 35 to 95 proteins, or about 35 to 90 proteins, or about 35 to 85 proteins, or about 35 to 80 proteins, or about 35 to 75 proteins, or about 35 to 70 proteins, or about 35 to 65 proteins, or about 35 to 60 proteins, or about 35 to 55 proteins, or about 35 to 50 proteins, or about 35 to 45 proteins, or about 35 to 40 proteins, or about 40 to 161 proteins, or about 40 to 160 proteins, or about 40 to 155 proteins, or about 40 to 150 proteins, or about 40 to 145 proteins, or about 40 to 140 proteins, or about 40 to 135 proteins, or about 40 to 130 proteins, or about 40 to 125 proteins, or about 40 to 120 proteins, or about 40 to 115 proteins, or about 40 to 110 proteins, or about 40 to 105 proteins, or about 40 to 100 proteins, or about 40 to 95 proteins, or about 40 to 90 proteins, or about 40 to 85 proteins, or about 40 to 80 proteins, or about 40 to 75 proteins, or about 40 to 70 proteins, or about 40 to 65 proteins, or about 40 to 60 proteins, or about 40 to 55 proteins, or about 40 to 50 proteins, or about 40 to 45 proteins, or about 45 to 161 proteins, or about 45 to 160 proteins, or about 45 to 155 proteins, or about 45 to 150 proteins, or about 45 to 145 proteins, or about 45 to 140 proteins, or about 45 to 135 proteins, or about 45 to 130 proteins, or about 45 to 125 proteins, or about 45 to 120 proteins, or about 45 to 115 proteins, or about 45 to 110 proteins, or about 45 to 105 proteins, or about 45 to100 proteins, or about 45 to 95 proteins, or about 45 to 90 proteins, or about 45 to 85 proteins, or about 45 to 80 proteins, or about 45 to 75 proteins, or about 45 to 70 proteins, or about 45 to 65 proteins, or about 45 to 60 proteins, or about 45 to 55 proteins, or about 45 to 50 proteins, or about 50 to 161 proteins, or about 50 to 160 proteins, or about 50 to 155 proteins, or about 50 to 150 proteins, or about 50 to 145 proteins, or about 50 to 140 proteins, or about 50 to 135 proteins, or about 50 to 130 proteins, or about 50 to 125 proteins, or about 50 to 120 proteins, or about 50 to 115 proteins, or about 50 to 110 proteins, or about 50 to 105 proteins, or about 50 to 100 proteins, or about 50 to 95 proteins, or about 50 to 90 proteins, or about 50 to 85 proteins, or about 50 to 80 proteins, or about 50 to 75 proteins, or about 50 to 70 proteins, or about 50 to 65 proteins, or about 50 to 60 proteins, or about 50 to 55 proteins, or about 55 to 161 proteins, or about 55 to 160 proteins, or about 55 to 155 proteins, or about 55 to 150 proteins, or about 55 to 145 proteins, or about 55 to 140 proteins, or about 55 to 135 proteins, or about 55 to 130 proteins, or about 55 to 125 proteins, or about 55 to 120 proteins, or about 55 to 115 proteins, or about 55 to 110 proteins, or about 55 to 105 proteins, or about 55 to 100 proteins, or about 55 to 95 proteins, or about 55 to 90 proteins, or about 55 to 85 proteins, or about 55 to 80 proteins, or about 55 to 75 proteins, or about 55 to 70 proteins, or about 55 to 65 proteins, or about 55 to 60 proteins, or about 60 to 161 proteins, or about 60 to 160 proteins, or about 60 to 155 proteins, or about 60 to 150 proteins, or about 60 to 145 proteins, or about 60 to 140 proteins, or about 60 to 135 proteins, or about 60 to 130 proteins, or about 60 to 125 proteins, or about 60 to 120 proteins, or about 60 to 115 proteins, or about 60 to 110 proteins, or about 60 to 105 proteins, or about 60 to 100 proteins, or about 60 to 95 proteins, or about 60 to 90 proteins, or about 60 to 85 proteins, or about 60 to 80 proteins, or about 60 to 75 proteins, or about 60 to 70 proteins, or about 60 to 65 proteins, or about 65 to 161 proteins, or about 65 to 160 proteins, or about 65 to 155 proteins, or about 65 to 150 proteins, or about 65 to 145 proteins, or about 65 to 140 proteins, or about 65 to 135 proteins, or about 65 to 130 proteins, or about 65 to 125 proteins, or about 65 to 120 proteins, or about 65 to 115 proteins, or about 65 to 110 proteins, or about 65 to 105 proteins, or about 65 to 100 proteins, or about 65 to 95 proteins, or about 65 to 90 proteins, or about 65 to 85 proteins, or about 65 to 80 proteins, or about 65 to 75 proteins, or about 65 to 70 proteins, or about 70 to 161 proteins, or about 70 to 160 proteins, or about 70 to 155 proteins, or about 70 to 150 proteins, or about 70 to 145 proteins, or about 70 to 140 proteins, or about 70 to 135 proteins, or about 70 to 130 proteins, or about 70 to 125 proteins,or about 70 to 120 proteins, or about 70 to 115 proteins, or about 70 to 110 proteins, or about 70 to 105 proteins, or about 70 to 100 proteins, or about 70 to 95 proteins, or about 70 to 90 proteins, or about 70 to 85 proteins, or about 70 to 80 proteins, or about 70 to 75 proteins, or about 75 to 161 proteins, or about 75 to 160 proteins, or about 75 to 155 proteins, or about 75 to 150 proteins, or about 75 to 145 proteins, or about 75 to 140 proteins, or about 75 to 135 proteins, or about 75 to 130 proteins, or about 75 to 125 proteins, or about 75 to 120 proteins, or about 75 to 115 proteins, or about 75 to 110 proteins, or about 75 to 105 proteins, or about 75 to 100 proteins, or about 75 to 95 proteins, or about 75 to 90 proteins, or about 75 to 85 proteins, or about 75 to 80 proteins, or about 80 to 161 proteins, or about 80 to 160 proteins, or about 80 to 155 proteins, or about 80 to 150 proteins, or about 80 to 145 proteins, or about 80 to 140 proteins, or about 80 to 135 proteins, or about 80 to 130 proteins, or about 80 to 125 proteins, or about 80 to 120 proteins, or about 80 to 115 proteins, or about 80 to 110 proteins, or about 80 to 105 proteins, or about 80 to 100 proteins, or about 80 to 95 proteins, or about 80 to 90 proteins, or about 80 to 85 proteins, or about 85 to 161 proteins, or about 85 to 160 proteins, or about 85 to 155 proteins, or about 85 to 150 proteins, or about 85 to 145 proteins, or about 85 to 140 proteins, or about 85 to 135 proteins, or about 85 to 130 proteins, or about 85 to 125 proteins, or about 85 to 120 proteins, or about 85 to 115 proteins, or about 85 to 110 proteins, or about 85 to 105 proteins, or about 85 to 100 proteins, or about 85 to 95 proteins, or about 85 to 90 proteins, or about 90 to 161 proteins, or about 90 to 160 proteins, or about 90 to 155 proteins, or about 90 to 150 proteins, or about 90 to 145 proteins, or about 90 to 140 proteins, or about 90 to 135 proteins, or about 90 to 130 proteins, or about 90 to 125 proteins, or about 90 to 120 proteins, or about 90 to 115 proteins, or about 90 to 110 proteins, or about 90 to 105 proteins, or about 90 to 100 proteins, or about 90 to 95 proteins, or about 95 to 161 proteins, or about 95 to 160 proteins, or about 95 to 155 proteins, or about 95 to 150 proteins, or about 95 to 145 proteins, or about 95 to 140 proteins, or about 95 to 135 proteins, or about 95 to 130 proteins, or about 95 to 125 proteins, or about 95 to 120 proteins, or about 95 to 115 proteins, or about 95 to 110 proteins, or about 95 to 105 proteins, or about 95 to 100 proteins, or about 100 to 161 proteins, or about 100 to 160 proteins, or about 100 to 155 proteins, or about 100 to 150 proteins, or about 100 to 145 proteins, or about 100 to 140 proteins, or about 100 to 135 proteins, or about 100 to 130 proteins, or about 100 to 125 proteins, or about 100 to 120 proteins, or about 100 to 115 proteins, or about 100 to 110 proteins, or about 100 to 105 proteins, or about 105 to 161 proteins, orabout 105 to 160 proteins, or about 105 to 155 proteins, or about 105 to 150 proteins, or about 105 to 145 proteins, or about 105 to 140 proteins, or about 105 to 135 proteins, or about 105 to 130 proteins, or about 105 to 125 proteins, or about 105 to 120 proteins, or about 105 to 115 proteins, or about 105 to 110 proteins, or about 110 to 161 proteins, or about 110 to 160 proteins, or about 110 to 155 proteins, or about 110 to 150 proteins, or about 110 to 145 proteins, or about 110 to 140 proteins, or about 110 to 135 proteins, or about 110 to 130 proteins, or about 110 to 125 proteins, or about 110 to 120 proteins, or about 110 to 115 proteins, or about 115 to 161 proteins, or about 115 to 160 proteins, or about 115 to 155 proteins, or about 115 to 150 proteins, or about 115 to 145 proteins, or about 115 to 140 proteins, or about 115 to 135 proteins, or about 115 to 130 proteins, or about 115 to 125 proteins, or about 115 to 120 proteins, or about 120 to 161 proteins, or about 120 to 160 proteins, or about 120 to 155 proteins, or about 120 to 150 proteins, or about 120 to 145 proteins, or about 120 to 140 proteins, or about 120 to 135 proteins, or about 120 to 130 proteins, or about 120 to 125 proteins, or about 125 to 161 proteins, or about 125 to 160 proteins, or about 125 to 155 proteins, or about 125 to 150 proteins, or about 125 to 145 proteins, or about 125 to 140 proteins, or about 125 to 135 proteins, or about 125 to 130 proteins, or about 130 to 161 proteins, or about 130 to 160 proteins, or about 130 to 155 proteins, or about 130 to 150 proteins, or about 130 to 145 proteins, or about 130 to 140 proteins, or about 130 to 135 proteins, or about 135 to 161 proteins, or about 135 to 160 proteins, or about 135 to 155 proteins, or about 135 to 150 proteins, or about 135 to 145 proteins, or about 135 to 140 proteins, or about 140 to 161 proteins, or about 140 to 160 proteins, or about 140 to 155 proteins, or about 140 to 150 proteins, or about 140 to 145 proteins, or about 145 to 161 proteins, or about 145 to 160 proteins, or about 145 to 150 proteins, or about 150 to 161 proteins, or about 150 to 160 proteins, or about 150 to 155 proteins, or about 155 to 161 proteins, or about 155 to 160 proteins, or about 160 to 161 proteins.

[0235] In some embodiments, the kit may also comprise one or more enzymes, substrates, labels, or other components useful for performing the assays.

[0236] In some embodiments, the kit further comprises one or more of the following: one or more containers for collecting or holding the sample (e.g., plasma sample), controls, directions for performing the methods, any necessary software for analysis and presentation of results.

[0237] One skilled in the art will readily recognize that the disclosed one or more components can be readily incorporated into any of the established kit formats that are well known in the art.EXAMPLE

[0238] Analyses were performed to identify the NSCLC detection proteins of the present invention.Sample CollectionPlasma samples were collected from a patient population diagnosed with NSCLC, and from healthy individuals without NSCLC.Protein Measurement

[0239] While any protein measurement technique could have been used, including enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), immunohistochemistry (IHC), liquid-bead immunoassays, mass spectrometry, aptamer-based assays, reverse phase protein arrays (RPPA), etc., a proximity extension assay (PEA) was employed to evaluate proteins in urine. In PEA, each protein was recognized by two antibodies for proper detection. In proximity assays, each of the two antibodies was conjugated to one of two different DNA oligonucleotides, and the reagents were incubated with the samples in solution. The proximity reactions underwent a dilution step.Oligonucleotides on pairs of antibodies that remain in proximity by virtue of having bound the same protein molecule then underwent DNA ligation (proximity ligation assay) or DNA polymerization (proximity extension assay). The effect of the ligation or polymerization reactions was to create amplifiable reporter DNA strands for sensitive readout via, for example, real-time PCR or next-generation sequencing, and the assays could be performed in high multiplex. By constructing the assays so that only proper pairs of antibodies can yield detection signals, but no other combination of antibodies, the detection of many different proteins in parallel was possible without eroding detection specificity by reactions of noncognate pairs.

[0240] The analytical performance of the panels was validated for sensitivity, dynamic range, specificity, precision, and scalability. The analytical measuring range was defined by the lower limit of quantification (LLOQ) and upper limit of quantification(ULOQ) and reported in pg / mL. The high dose hook effect (a state of antigen excess relative to the reagent antibodies resulting in falsely lower values) was also determined for each analyte.

[0241] All assays were thoroughly validated for precision (repeatability and reproducibility). Intra-assay variation (within-run) was calculated as the mean CV for individual samples, within each of separate runs during the validation studies. Inter-assay variation (between-runs) was calculated as the mean CV, for the same individual samples, among separate runs during the validation studies.

[0242] Each protein analyte was addressed by a matched pair of antibodies, coupled to unique, partially complementary oligonucleotides and measured by quantitative real-time PCR. Validation of the readout specificity for all of the panels was carried out using a simple, sequential approach in which pools of protein analytes were tested.Feature Selection

[0243] Proteins were used to create features that could be used for the classification of samples. The proteins were categorized based on their concentration or their patterns of change detected by different statistical or machine-learning techniques to create new features.

[0244] Machine learning and statistical analyses techniques used to generate features and the final score for the cancer were included but not limited to the following concepts and methods: supervised learning concepts that may include AODE; artificial neural network, such as Backpropagation, Auto encoders, Hopfield networks, Boltzmann machines, Restricted Boltzmann Machines, and Spiking neural networks; Bayesian statistics, such as Bayesian network and Bayesian knowledge base; case-based reasoning; Gaussian process regression; gene expression programming; group method of data handling (GMDH); inductive logic programming; instance-based learning; lazy learning; learning Automata; learning vector quantization; logistic model tree; minimum message length (decision trees, decision graphs, etc.), such as nearest neighbor algorithm and analogical modeling; probability approximately correct learning (PAC) learning; ripple down rules, a knowledge acquisition methodology; symbolic machine learning algorithms; support vector machines; random forests; ensembles of classifiers, such as bootstrap aggregating (bagging) and boosting (meta -algorithm ); ordinal classification; information fuzzy networks (IFN); conditional random field; ANOVA; linear classifiers, such’as Fisher's linear discriminant,linear regression, logistic regression, multinomial logistic relion, naive Bayes classifier, Perceptron, support vector machines; quadratic classifiers; k -nearest neighbor; boosting; decision trees, such as C4.5, random forests, ID3, CART, SLIQ SPRINT; Bayesian netl, such as Naive Bayes; and Hidden Markov models. cUnsupervised learning concepts may include; expectation -maximization algorithm; vector quantization; generative topographic map; information bottleneck method; artificial neural network, such as self -organizing map; association rule learning, such as Apriori algorithm, Eclat algorithm, and FP growth algorithm; hierarchical clusterings such as single linkage clustering and conceptual clustering; cluster analysis, such as K -means algorithm, fuzzy clustering, DBSCAN, and OPTICS algorithm; and outlier detection, such as local outlier factor. Semi -supervised learning concepts may include: generative models; low-density separation; graph-based methods, and co -training. Reinforcement learning concepts may include temporal difference learning; Q -learning, learning automata, and SARSA. Deep learning concepts may include deep belief networks; deep Boltzmann machines; deep convolutional neural networks; deep recurrent neural networks; and hierarchical temporal memory.Detection Proteins

[0245] One or more features were fed into one or more computation models. The classifiers were used to calculate a score for the patient. The scores of different classifiers were combined to identify the patient as having NSCLC or not; as having SCLC or not; or as having lung cancer that can be either NSCLC or SCLC, or not. The computational model only selected protein or protein combinations that could generate a receiver operating characteristic (ROC) curve of greater than or equal to 0.6.

[0246] Table 1 lists proteins that can detect NSCLC in subjects of either gender. In particular, Table l.A shows a full list of the NSCLC detction proteins and their individual AUC, and Table l.B, Table l.C, Table l.D, Table l.E, Table l.F, and Table l.G show partticular subsets of proteins of Table LA. Analysis of the proteins in Table l.A showed that the accuracy for detecting NSCLC was over 0.70 when any two proteins through any 15 proteins were randomly selected (see FIG. 1). Further, a panel of all proteins in Table 1.A was shown to have high diagnostic utility in detecting NSCLC, as the AUC of ROC curves generated using two different classifiers — a first classifier and a second classifier — was each over 0.94 (see FIG. 2, Panels A and B). Simiarly, a panel of all proteins in the subsetsshown in Table l.B, Table l.C, Table l.D, Table l.E, Table 1.F, and Table l.G also exhibited high diagnostic utiltiy, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.90, as shown in FIGS. 3-8, respectively, and in Table 10.

[0247] Table 2 lists proteins that can detect NSCLC in female subjects. Table 2.A shows a full list of the NSCLC detction proteins for female subjects and their individual AUC, and Table 2.B, Table 2.C, Table 2.D, Table 2.E, Table 2.F, and Table 2.G show subsets of proteins of Table 2.A. Analysis of the proteins in Table 2.A showed that the accuracy for detecting NSCLC was over 0.70 when any two proteins through any 15 proteins were selected randomly (see FIG. 9). Further, a panel of all proteins in Table 2.A was shown to have high diagnostic utility in detecting NSCLC; the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve generated by the second classifier was each over 0.90 (see FIG. 10, Panels A and B). In addition, a panel of all proteins in the subsets shown in Table 2.B, Table 2.C, Table 2.D, Table 2.E, Table 2.F, and Table 2.G exhibited high diagnostic utiltiy as well, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.87, as shown in FIGS. 11-16, respectively, and in Table 11.

[0248] Table 3 lists proteins that can detect NSCLC in male subjects. Table 3.A shows a full list of the NSCLC detction proteins for male subjects and their individual AUC, and Table 3.B, Table 3.C, Table 3.D, Table 3.E, Table 3.F, and Table 3.G show subsets of proteins of Table 3.A. Analysis of the proteins in Table 3.A showed that the accuracy for detecting NSCLC was over 0.70 when any two proteins through any 15 proteins are randomly selected (see FIG. 17). Moreover, a panel of all proteins in Table 3.A was shown to have high diagnostic utility in detecting NSCLC, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve generated by the second classifier was each over 0.96 (see FIG. 18, Panels A and B). In addition, a panel of all proteins in the subsets shown in Table 3.B, Table 3.C, Table 3.D, Table 3.E, Table 3.F, and Table 3.G exhibited high diagnostic utiltiy, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.87, as shown in FIGS. 19-24, respectively, and in Table 12.

[0249] Table 4 lists proteins that can detect SCLC in subjects of either gender. In particular, Table 4. A shows a full list of the SCLC detction proteins for subjects of either gender and their individual AUC, and Table 4.B, Table 4.C, Table 4.D, Table 4.E, Table 4.F, and Table 4.G show partticular subsets of proteins of Table 4.A. Analysis of the proteins in Table 4. A showed that the accuracy for detecting SCLC was over 0.60 when any two proteins through any 15 proteins were randomly selected (see FIG. 25). Further, a panel of all proteins in Table 4.A was shown to have high diagnostic utility in detecting NSCLC, as the AUC of ROC curves generated using the first classifier and the second classifier was each over 0.88 (see FIG. 26, Panels A and B). Simiarly, a panel of all proteins in the subsets shown in Table 4.B, Table 4.C, Table 4.D, Table 4.E, Table 4.F, and Table 4.G also exhibited high diagnostic utiltiy, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.81, as shown in FIGS. 27-32, respectively, and in Table 13.

[0250] Table 5 lists proteins that can detect SCLC in female subjects. Table 5.A shows a full list of the SCLC detction proteins for female subjects and their individual AUC, and Table 5.B, Table 5.C, Table 5.D, Table 5.E, Table 5.F, and Table 5.G show subsets of proteins of Table 5.A. Analysis of the proteins in Table 5.A showed that the accuracy for detecting SCLC was over 0.65 when any two proteins through any 15 proteins were selected randomly (see FIG. 33). Further, a panel of all proteins in Table 5.A was shown to have high diagnostic utility in detecting SCLC; the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve generated by the second classifier was each over 0.95 (see FIG. 34, Panels A and B). In addition, a panel of all proteins in the subsets shown in Table 5.B, Table 5.C, Table 5.D, Table 5.E, Table 5.F, and Table 5.G exhibited high diagnostic utiltiy as well, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.82, as shown in FIGS. 35-40, respectively, and in Table 14.

[0251] Table 6 lists proteins that can detect SCLC in male subjects. Table 6. A shows a full list of the SCLC detction proteins for male subjects and their individual AUC, and Table 6.B, Table 6.C, Table 6.D, Table 6.E, Table 6.F, and Table 6.G show subsets of proteins of Table 6.A. Analysis of the proteins in Table 6.A showed that the accuracy for detecting SCLC was over 0.70 when any two proteins through any 15 proteins are randomly selected (see FIG. 41). Moreover, a panel of all proteins in Table 6.A was shown to havehigh diagnostic utility in detecting SCLC, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve generated by the second classifier was each over 0.85 (see FIG. 42, Panels A and B). In addition, a panel of all proteins in the subsets shown in Table 6.B, Table 6.C, Table 6.D, Table 6.E, Table 6.F, and Table 6.G exhibited high diagnostic utiltiy, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.89, as shown in FIGS. 43-48, respectively, and in Table 15.

[0252] Table 7 lists proteins that can detect lung cancer that is either NSCLC or SCLC in subjects of either gender. In particular, Table 7.A shows a full list of the general lung cancer detction proteins for subjects of either gender and their individual AUC, and Table 7.B, Table 7.C, Table 7.D, Table 7.E, Table 7.F, and Table 7.G show partticular subsets of proteins of Table 7.A. Analysis of the proteins in Table 7.A showed that the accuracy for detecting lung cancer that is either NSCLC or SCLC was over about 0.70 when any two proteins through any 15 proteins were randomly selected (see FIG. 49). Further, a panel of all proteins in Table 7. A was shown to have high diagnostic utility in detecting lung cancer that is either NSCLC or SCLC, as the AUC of ROC curves generated using the first classifier and the second classifier was each over 0.92 (see FIG. 50, Panels A and B). Simiarly, a panel of all proteins in the subsets shown in Table 7.B, Table 7.C, Table 7.D, Table 7.E, Table 7.F, and Table 7.G also exhibited high diagnostic utiltiy, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.88, as shown in FIGS. 51-56, respectively, and in Table 16.

[0253] Table 8 lists proteins that can detect lung cancer that is either NSCLC or SCLC in female subjects. Table 8.A shows a full list of the general lung cancer detction proteins for female subjects and their individual AUC, and Table 8.B, Table 8.C, Table 8.D, Table 8.E, Table 8.F, and Table 8.G show subsets of proteins of Table 8.A. Analysis of the proteins in Table 8. A showed that the accuracy for detecting lung cancer that is either NSCLC or SCLC was over 0.70 when any two proteins through any 15 proteins were selected randomly (see FIG. 57). Further, a panel of all proteins in Table 8.A was shown to have high diagnostic utility in detecting lung cancer that is either NSCLC or SCLC; the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve generated by the second classifier was each over 0.87 (see FIG. 58, Panels A and B). In addition, a panelof all proteins in the subsets shown in Table 8.B, Table 8.C, Table 8.D, Table 8.E, Table8.F, and Table 8.G exhibited high diagnostic utiltiy as well, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.84, as shown in FIGS. 59-64, respectively, and in Table 17.

[0254] Table 9 lists proteins that can detect lung cancer that is either NSCLC or SCLC in male subjects. Table 9.A shows a full list of the general lung cancer detction proteins for male subjects and their individual AUC, and Table 9.B, Table 9.C, Table 9.D, Table 9.E, Table 9.F, and Table 9.G show subsets of proteins of Table 9.A. Analysis of the proteins in Table 9. A showed that the accuracy for detecting lung cancer that is either NSCLC or SCLC was over 0.70 when any two proteins through any 15 proteins are randomly selected (see FIG. 65). Moreover, a panel of all proteins in Table 9.A was shown to have high diagnostic utility in detecting lung cancer that is either NSCLC or SCLC, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve generated by the second classifier was each over 0.95 (see FIG. 66, Panels A and B). In addition, a panel of all proteins in the subsets shown in Table 9.B, Table 9.C, Table 9.D, Table 9.E, Table9.F, and Table 9.G exhibited high diagnostic utiltiy, as the AUC of a ROC curve generated using the first classifier and the AUC of a ROC curve geneated by the second classifier were each over 0.91, as shown in FIGS. 67-72, respectively, and in Table 18.Table 1. Proteins for detection of NSCLC in subjects of either gender.Table 2. Proteins for detection of NSCLC in female subjects.Table 3. Proteins for detection of NSCLC in male subjects.Table 4. Proteins for detection of SCLC in subjects of either gender.Table 5. Proteins for detection of SCLC in female subjects.Table 6. Proteins for detection of SCLC in male subjects.Table 7. Proteins for detection of lung cancer that is either NSCLC or SCLC, in subjects of either gender.Table 8. Proteins for detection of lung cancer that is either NSCLC or SCLC, in female subjects.Table 9. Proteins for detection of lung cancer that is either NSCLC or SCLC, in male subjects.Table 10. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table l.A - Table l.G for detecting NSCLC in subjects.Table 11. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table l.A - Table l.G for detecting NSCLC in female subjects.Table 12. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 3.A - Table 3.G for detecting NSCLC in male subjects.Table 13. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 4.A - Table 4.G for detecting SCLC in subjects.Table 14. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 5.A - Table 5.G for detecting SCLC in female subjects.Table 15. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 6.A - Table 6.G for detecting SCLC in male subjects.Table 16. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 7.A - Table 7.G for detecting lung cancer (NSCLC or SCLC) in subjects.Table 17. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 8.A - Table 8.G for detecting lung cancer (NSCLC or SCLC) in female subjects.Table 18. AUC of ROC curves generated by application of the first classifier and the second classifier using the protein panels set forth in Table 9.A - Table 9.G for detecting lung cancer (NSCLC or SCLC) in male subjects.EMBODIMENTS

[0255] Select embodiments of the present invention are as follows:Embodiment 1. A method of evaluating a subject for NSCLC, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; thereby evaluating the subject for cancer.Embodiment 2. The method of Embodiment 1, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having NSCLC.Embodiment 3. The method of Embodiment 1 or 2, further comprising administering a treatment to the subject.Embodiment 4. A method of treating NSCLC in a subject, comprising(a) acquiring results from the method of Embodiments 1 or 2; and(b) administering a treatment to the subject.Embodiment 5. The method of Embodiment 4, wherein the treatment is responsive to the results acquired in (a).Embodiment 6. The method of Embodiment 4 or 5, wherein (a) comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has NSCLC.Embodiment 7. A method of treating NSCLC in a subject, the method comprising:(a) acquiring results from an evaluation of the subject that determined the subject has NSCLC;(b) administering a treatment to the subject, wherein the evaluation comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has NSCLC.Embodiment 8. The method of any one of Embodiments 4-7, wherein the results in (a) are acquired from a third party.Embodiment 9. A method of detecting NSCLC in a subject, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.Embodiment 10. The method of Embodiment 9, further comprising administering a treatment to the subject.Embodiment 11. A method of treating NSCLC in a subject, comprising(a) acquiring results from the method of Embodiment 9; and(b) administering a treatment to the subject.Embodiment 12. The method of Embodiment 11, wherein the treatment is responsive to the results acquired in (a).Embodiment 13. A method of treating NSCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected; and administering a treatment to the subject when NSCLC is detected.Embodiment 14. A method of treating NSCLC in a subject in whom NSCLC was detected, the method comprising administering a treatment for NSCLC to the subject, wherein NSCLC was detected in the subject by a method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.Embodiment 15. The method of Embodiment 14, wherein the method of detecting NSCLC was performed by a third party.Embodiment 16. The method of any one of Embodiments 1-15, wherein the NSCLC is early-stage.Embodiment 17. The method of any one of Embodiments 1-15, wherein the NSCLC is late- stage.Embodiment 18. The method of any one of Embodiments 1-15, wherein the subject is asymptomatic of NSCLC.Embodiment 19. The method of any one of Embodiments 1-15, wherein the subject is undergoing a screen for NSCLC.Embodiment 20. The method of any one of Embodiments 1-15, wherein the subject is symptomatic of NSCLC.Embodiment 21. A method of evaluating a treatment for NSCLC in a subject, the method comprising:(a) administering a treatment for NSCLC, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; thereby evaluating the treatment.Embodiment 22. A method of evaluating the efficacy of a treatment for NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; thereby evaluating the efficacy of the treatment.Embodiment 23. A method of treating NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.Embodiment 24. A method of adjusting a treatment for NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject,(b) determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 1, or from Table 2, or from Table 3, and(c) administering an adjusted treatment to the subject when it is determined that the adjusted treatment is necessary.Embodiment 25. A method of treating NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.Embodiment 26. The method of Embodiment 25, further comprising administering an adjusted treatment when it is determined that the adjusted treatment is necessary.Embodiment 27. A method of monitoring for NSCLC recurrence in a subject, comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the NSCLC is recurring, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.Embodiment 28. A method of treating NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.Embodiment 29. The method of Embodiment 27 or 28, further comprising administering a second treatment when it is determined that the cancer is recurring.Embodiment 30. The method of any one of Embodiments 21-29, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having NSCLC.Embodiment 31. The method of any one of Embodiments 1-30, wherein the one or more proteins are selected from Table 1.Embodiment 32. The method of Embodiment 31, wherein the one or more proteins are selected from Table 1.A, Table l.B, Table l.C, Table l.D, Table l.E, or Table 1.F,Embodiment 33. The method of any one of Embodiments 1-31, wherein the one or more proteins comprise at least the proteins of Table l.G.Embodiment 34. The method of any one of Embodiments 1-30, wherein the subject is female.Embodiment 35. The method of Embodiment 34, wherein the one or more proteins are selected from Table 2.Embodiment 36. The method of Embodiment 35, wherein the one or more proteins are selected from Table 2.A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F,Embodiment 37. The method of Embodiments 34 or 35, wherein the one or more proteins comprise at least the proteins of Table 2.G.Embodiment 38. The method of any one of Embodiments 1-30, wherein the subject is male.Embodiment 39. The method of Embodiment 38, wherein the one or more proteins are selected from Table 3.Embodiment 40. The method of Embodiment 35, wherein the one or more proteins are selected from Table 3.A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F.Embodiment 41. The method of Embodiments 38 or 39, wherein the one or more proteins comprise at least the proteins of Table 3.G.Embodiment 42. A method of evaluating a subject for SCLC, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; thereby evaluating the subject for cancer.Embodiment 43. The method of Embodiment 42, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having SCLC.Embodiment 44. The method of Embodiment 42 or 43, further comprising administering a treatment to the subject.Embodiment 45. A method of treating SCLC in a subject, comprising(a) acquiring results from the method of Embodiments 42 or 43; and(b) administering a treatment to the subject.Embodiment 46. The method of Embodiment 45, wherein the treatment is responsive to the results acquired in (a).Embodiment 47. The method of Embodiment 45 or 46, wherein (a) comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has SCLC.Embodiment 48. A method of treating SCLC in a subject, the method comprising:(a) acquiring results from an evaluation of the subject that determined the subject has SCLC;(b) administering a treatment to the subject, wherein the evaluation comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has SCLC.Embodiment 49. The method of any one of Embodiments 45-48, wherein the results in (a) are acquired from a third party.Embodiment 50. A method of detecting SCLC in a subject, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.Embodiment 51. The method of Embodiment 50, further comprising administering a treatment to the subject.Embodiment 52. A method of treating SCLC in a subject, comprising(a) acquiring results from the method of Embodiment 39; and(b) administering a treatment to the subject.Embodiment 53. The method of Embodiment 52, wherein the treatment is responsive to the results acquired in (a).I l lEmbodiment 54. A method of treating SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected; and administering a treatment to the subject when SCLC is detected.Embodiment 55. A method of treating SCLC in a subject in whom SCLC was detected, the method comprising administering a treatment for SCLC to the subject, wherein SCLC was detected in the subject by a method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.Embodiment 56. The method of Embodiment 55, wherein the method of detecting SCLC was performed by a third party.Embodiment 57. The method of any one of Embodiments 42-56, wherein the NSCLC is early-stage.Embodiment 58. The method of any one of Embodiments 42-56, wherein the NSCLC is late- stage.Embodiment 59. The method of any one of Embodiments 42-56, wherein the subject is asymptomatic of NSCLC.Embodiment 60. The method of any one of Embodiments 42-56, wherein the subject is undergoing a screen for SCLC.Embodiment 61. The method of any one of Embodiments 42-56, wherein the subject is symptomatic of SCLC.Embodiment 62. A method of evaluating a treatment for SCLC in a subject, the method comprising:(a) administering a treatment for SCLC, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; thereby evaluating the treatment.Embodiment 63. A method of evaluating the efficacy of a treatment for SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; thereby evaluating the efficacy of the treatment.Embodiment 64. A method of treating SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.Embodiment 65. A method of adjusting a treatment for SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject,(b) determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 4, or from Table 5, or from Table 6, and(c) administering an adjusted treatment to the subject when it is determined that the adjusted treatment is necessary.Embodiment 66. A method of treating SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.Embodiment 67. The method of Embodiment 66, further comprising administering an adjusted treatment when it is determined that the adjusted treatment is necessary.Embodiment 68. A method of monitoring for SCLC recurrence in a subject, comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the SCLC is recurring, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.Embodiment 69. A method of treating SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.Embodiment 70. The method of Embodiment 68 or 69, further comprising administering a second treatment when it is determined that the cancer is recurring.Embodiment 71. The method of any one of Embodiments 62-70, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having SCLC.Embodiment 72. The method of any one of Embodiments 42-71, wherein the one or more proteins are selected from Table 4.Embodiment 73. The method of Embodiment 72, wherein the one or more proteins are selected from Table 4.A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F.Embodiment 74. The method of any one of Embodiments 42-72, wherein the one or more proteins comprise at least the proteins of Table 4.G.Embodiment 75. The method of any one of Embodiments 42-71, wherein the subject is female.Embodiment 76. The method of Embodiment 75, wherein the one or more proteins are selected from Table 5.Embodiment 77. The method of Embodiment 76, wherein the one or more proteins are selected from Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F.Embodiment 78. The method of Embodiments 75 or 76, wherein the one or more proteins comprise at least the proteins of Table 5.G.Embodiment 79. The method of any one of Embodiments 42-71, wherein the subject is male.Embodiment 80. The method of Embodiment 79, wherein the one or more proteins are selected from Table 6.Embodiment 81. The method of Embodiment 80, wherein the one or more proteins are selected from Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F.Embodiment 82. The method of Embodiments 79 or 80, wherein the one or more proteins comprise at least the proteins of Table 6.G.Embodiment 83. A method of evaluating a subject for lung cancer that is either NSCLC or SCLC, the method comprising:determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; thereby evaluating the subject for cancer.Embodiment 84. The method of Embodiment 83, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having lung cancer.Embodiment 85. The method of Embodiment 83 or 84, further comprising administering a treatment to the subject.Embodiment 86. A method of treating lung cancer that is either NSCLC or SCLC in a subject, comprising(a) acquiring results from the method of Embodiments 61 or 62; and(b) administering a treatment to the subject.Embodiment 87. The method of Embodiment 86, wherein the treatment is responsive to the results acquired in (a).Embodiment 88. The method of Embodiment 86 or 87, wherein (a) comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has lung cancer.Embodiment 89. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising:(a) acquiring results from an evaluation of the subject that determined the subject has lung cancer;(b) administering a treatment to the subject, wherein the evaluation comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has lung cancer.Embodiment 90. The method of any one of Embodiments 86-89, wherein the results in (a) are acquired from a third party.Embodiment 91. A method of detecting lung cancer that is either NSCLC or SCLC in a subject, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.Embodiment 92. The method of Embodiment 91, further comprising administering a treatment to the subject.Embodiment 93. A method of treating lung cancer that is either NSCLC or SCLC in a subject, comprising(a) acquiring results from the method of Embodiment 91; and(b) administering a treatment to the subject.Embodiment 94. The method of Embodiment 93, wherein the treatment is responsive to the results acquired in (a).Embodiment 95. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected; and administering a treatment to the subject when lung cancer is detected.Embodiment 96. A method of treating lung cancer that is either NSCLC or SCLC in a subject in whom lung cancer was detected, the method comprising administering a treatment for lung cancer to the subject, wherein lung cancer was detected in the subject by a method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.Embodiment 97. The method of Embodiment 96, wherein the method of detecting lung cancer was performed by a third party.Embodiment 98. The method of any one of Embodiments 83-97, wherein the lung cancer is early-stage.Embodiment 99. The method of any one of Embodiments 83-97, wherein the lung cancer is late-stage.Embodiment 100. The method of any one of Embodiments 83-97, wherein the subject is asymptomatic of lung cancer.Embodiment 101. The method of any one of Embodiments 83-97, wherein the subject is undergoing a screen for lung cancer.Embodiment 102. The method of any one of Embodiments 83-97, wherein the subject is symptomatic of lung cancer.Embodiment 103. A method of evaluating a treatment for lung cancer that is either NSCLC or SCLC in a subject, the method comprising:(a) administering a treatment for lung cancer, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; thereby evaluating the treatment.Embodiment 104. A method of evaluating the efficacy of a treatment for lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; thereby evaluating the efficacy of the treatment.Embodiment 105. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.Embodiment 106. A method of adjusting a treatment for lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject,(b) determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 7, or from Table 8, or from Table 9, and(c) administering an adjusted treatment to the subject when it is determined that the adjusted treatment is necessary.Embodiment 107. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.Embodiment 108. The method of Embodiment 107, further comprising administering an adjusted treatment when it is determined that the adjusted treatment is necessary.Embodiment 109. A method of monitoring for lung cancer that is either NSCLC or SCLC recurrence in a subject, comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the lung cancer is recurring, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.Embodiment 110. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.Embodiment 111. The method of Embodiment 109 or 110, further comprising administering a second treatment when it is determined that the cancer is recurring.Embodiment 112. The method of any one of Embodiments 103-111, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having lung cancer.Embodiment 113. The method of any one of Embodiments 83-112, wherein the one or more proteins are selected from Table 4.Embodiment 114. The method of Embodiment 113, wherein the one or more proteins are selected from Table 4.A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F,Embodiment 115. The method of any one of Embodiments 83-113, wherein the one or more proteins comprise at least the proteins of Table 4.G.Embodiment 116. The method of any one of Embodiments 83-112, wherein the subject is female.Embodiment 117. The method of Embodiment 116, wherein the one or more proteins are selected from Table 5.Embodiment 118. The method of Embodiment 117, wherein the one or more proteins are selected from Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F.Embodiment 119. The method of Embodiments 116 or 117, wherein the one or more proteins comprise at least the proteins of Table 5.G.Embodiment 120. The method of any one of Embodiments 83-112, wherein the subject is male.Embodiment 121. The method of Embodiment 120, wherein the one or more proteins are selected from Table 6.Embodiment 122. The method of Embodiment 121, wherein the one or more proteins are selected from Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F.Embodiment 123. The method of Embodiments 120 or 121, wherein the one or more proteins comprise at least the proteins of Table 6.G.Embodiment 124. The method of any one of Embodiments 1-123, wherein the biological sample is selected from a plasma sample, serum sample, saliva sample, CSF sample, sweat sample, urine sample, or tear sample.Embodiment 125. The method of Embodiment 124, wherein the biological sample is a plasma sample.Embodiment 126. The method of any one of Embodiments 1-125, further comprising collecting the biological sample from the subject.Embodiment 127. The method of Embodiment 126, wherein the collection of the biological sample is performed in the home of the subject.Embodiment 128. The method of Embodiment 127, wherein the collection of the biological sample is performed in a medical facility.Embodiment 129. The method of any one of Embodiments 1-128, wherein the determination of the concentration of the one or more proteins is performed in the home of the subject.Embodiment 130. The method of any one of Embodiments 1-128, wherein the determination of the concentration of the one or more proteins is performed in a medical facility.Embodiment 131. The method of any one of Embodiments 1-130, wherein the number of proteins for which the concentration is determined is sufficient to achieve an AUC of a ROC curve of at least about 0.6.Embodiment 132. The method of Embodiment 131, wherein the number of proteins for which the concentration is determined is sufficient to achieve an AUC of a ROC curve of at least about 0.7.Embodiment 133. The method of Embodiment 132, wherein the number of proteins for which the concentration is determined is sufficient to achieve an AUC of a ROC curve of at least about 0.8.Embodiment 134. The method of any one of Embodiments 1-133, wherein the concentration of the two or more proteins is determined by one or more assays.Embodiment 135. The method of any one of Embodiments 21-30, 62-71, or 103-112, wherein the administration of the treatment in (a) is performed by a third party.Embodiment 136. The method of any one of Embodiments 21-30, 62-71, or 103-112, wherein the determination in the biological sample from the subject a concentration of one or more proteins in (b) is performed by a third party.Embodiment 137. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 1.Embodiment 138. The method of Embodiment 137, wherein the one or more proteins are selected from Table 1.A, Table l.B, Table l.C, Table l.D, Table l.E, or Table 1.F,Embodiment 139. The method of Embodiment 137, wherein the one or more proteins are at least the proteins of Table l.G.Embodiment 140. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 2.Embodiment 141. The method of Embodiment 140, wherein the one or more proteins are selected from Table 2.A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F,Embodiment 142. The method of Embodiment 140, wherein the one or more proteins are at least the proteins of Table 2.G.Embodiment 143. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 3.Embodiment 144. The method of Embodiment 143, wherein the one or more proteins are selected from Table 3.A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F.Embodiment 145. The method of Embodiment 143, wherein the one or more proteins are at least the proteins of Table 3.G.Embodiment 146. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 4.Embodiment 147. The method of Embodiment 146, wherein the one or more proteins are selected from Table 4.A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F,Embodiment 148. The method of Embodiment 146, wherein the one or more proteins are at least the proteins of Table 4.G.Embodiment 149. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 5.Embodiment 150. The method of Embodiment 149, wherein the one or more proteins are selected from Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F.Embodiment 151. The method of Embodiment 149, wherein the one or more proteins are at least the proteins of Table 5.G.Embodiment 152. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 6.Embodiment 153. The method of Embodiment 152, wherein the one or more proteins are selected from Table 6.A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F.Embodiment 154. The method of Embodiment 152, wherein the one or more proteins are at least the proteins of Table 6.G.Embodiment 155. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 7.Embodiment 156. The method of Embodiment 155, wherein the one or more proteins are selected from Table 7.A, Table 7.B, Table 7.C, Table 7.D, Table 7.E, or Table 7.F,Embodiment 157. The method of Embodiment 155, wherein the one or more proteins are at least the proteins of Table 7.G.Embodiment 158. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 8.Embodiment 159. The method of Embodiment 158, wherein the one or more proteins are selected from Table 8.A, Table 8.B, Table 8.C, Table 8.D, Table 8.E, or Table 8.F.Embodiment 160. The method of Embodiment 158, wherein the one or more proteins are at least the proteins of Table 8.G.Embodiment 161. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 9.Embodiment 162. The method of Embodiment 161, wherein the one or more proteins are selected from Table 9.A, Table 9.B, Table 9.C, Table 9.D, Table 9.E, or Table 9.F.Embodiment 163. The method of Embodiment 161, wherein the one or more proteins are at least the proteins of Table 9.G.Embodiment 164. The method of any one of Embodiments 1-163, wherein two or more proteins are selected.Embodiment 165. The method of any one of Embodiments 1-164, wherein three or more proteins are selected.Embodiment 166. The method of any one of Embodiments 1-65, wherein five or more proteins are selected.Embodiment 167. The method of any one of Embodiments 1-66, wherein ten or more proteins are selected.Embodiment 168. The method of any one of Embodiments 1-167, wherein 20 or more proteins are selected.Embodiment 169. The method of any one of Embodiments 1-168, wherein 30 or more proteins are selected.Embodiment 170. The method of any one of Embodiments 1-169, wherein all proteins are selected.Embodiment 171. The method of any one of Embodiments 1-163, wherein no more than about 30 proteins are selected.Embodiment 172. The method of any one of Embodiments 1-163, wherein no more than about 20 proteins are selected.Embodiment 173. The method of any one of Embodiments 1-163, wherein no more than about ten proteins are selected.Embodiment 174. The method of any one of Embodiments 1-163, wherein no more than about five proteins are selected.REFERENCESAmerican Cancer Society, Cancer Facts & Figures 2023(https: / / www.cancer.org / content / dam / cancer-org / research / cancer-facts-and-statistics / annual- cancer-facts-and-figures / 2023 / 2023 -cancer-facts-and-figures.pdf), accessed on December 21, 2023.Manser R.L., et al.. Screening for lung cancer, Cochrane Database of Systemic Reviews, 2004, (1): CD001991.Nooreldeen R. and Bach H., Current and future development in lung cancer diagnosis, International Journal of Molecular Sciences, 2021, 22(16): 8661.Siegel R.L., et al., Cancer statistics, 2023, CA Cancer Journal for Clinicians, 2023, 73(1): 17-48.Sung H, et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer Journal for Clinicians, 2021, 71(3): 209-249.

Claims

CLAIMS1. A method of evaluating a subject for NSCLC, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; thereby evaluating the subject for cancer.

2. The method of claim 1, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having NSCLC.

3. The method of claim 1 or 2, further comprising administering a treatment to the subject.

4. A method of treating NSCLC in a subject, comprising(a) acquiring results from the method of claims 1 or 2; and(b) administering a treatment to the subject.

5. The method of claim 4, wherein the treatment is responsive to the results acquired in (a).

6. The method of claim 4 or 5, wherein (a) comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has NSCLC.

7. A method of treating NSCLC in a subject, the method comprising:(a) acquiring results from an evaluation of the subject that determined the subject has NSCLC;(b) administering a treatment to the subject, wherein the evaluation comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has NSCLC.

8. The method of any one of claims 4-7, wherein the results in (a) are acquired from a third party.

9. A method of detecting NSCLC in a subject, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.

10. The method of claim 9, further comprising administering a treatment to the subject.

11. A method of treating NSCLC in a subject, comprising(a) acquiring results from the method of claim 9; and(b) administering a treatment to the subject.

12. The method of claim 11, wherein the treatment is responsive to the results acquired in (a).

13. A method of treating NSCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected; and administering a treatment to the subject when NSCLC is detected.

14. A method of treating NSCLC in a subject in whom NSCLC was detected, the method comprising administering a treatment for NSCLC to the subject, wherein NSCLC was detected in the subject by a method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that NSCLC is detected.

15. The method of claim 14, wherein the method of detecting NSCLC was performed by a third party.

16. The method of any one of claims 1-15, wherein the NSCLC is early-stage.

17. The method of any one of claims 1-15, wherein the NSCLC is late-stage.

18. The method of any one of claims 1-15, wherein the subject is asymptomatic ofNSCLC.

19. The method of any one of claims 1-15, wherein the subject is undergoing a screen for NSCLC.

20. The method of any one of claims 1-15, wherein the subject is symptomatic of NSCLC.

21. A method of evaluating a treatment for NSCLC in a subject, the method comprising:(a) administering a treatment for NSCLC, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; thereby evaluating the treatment.

22. A method of evaluating the efficacy of a treatment for NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 1, or from Table 2, or from Table 3; thereby evaluating the efficacy of the treatment.

23. A method of treating NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.

24. A method of adjusting a treatment for NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject,(b) determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 1, or from Table 2, or from Table 3, and(c) administering an adjusted treatment to the subject when it is determined that the adjusted treatment is necessary.

25. A method of treating NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.

26. The method of claim 25, further comprising administering an adjusted treatment when it is determined that the adjusted treatment is necessary.

27. A method of monitoring for NSCLC recurrence in a subject, comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the NSCLC is recurring, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.

28. A method of treating NSCLC in a subject, the method comprising(a) administering a treatment for NSCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 1, or from Table 2, or from Table 3.

29. The method of claim 27 or 28, further comprising administering a second treatment when it is determined that the cancer is recurring.

30. The method of any one of claims 21-29, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having NSCLC.

31. The method of any one of claims 1-30, wherein the one or more proteins are selected from Table 1.

32. The method of claim 31, wherein the one or more proteins are selected from Table LA, Table LB, Table l.C, Table l.D, Table l.E, or Table l.F.

33. The method of any one of claims 1-31, wherein the one or more proteins comprise at least the proteins of Table LG.

34. The method of any one of claims 1-30, wherein the subject is female.

35. The method of claim 34, wherein the one or more proteins are selected from Table 2.

36. The method of claim 35, wherein the one or more proteins are selected from Table 2. A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F.

37. The method of claims 34 or 35, wherein the one or more proteins comprise at least the proteins of Table 2.G.

38. The method of any one of claims 1-30, wherein the subject is male.

39. The method of claim 38, wherein the one or more proteins are selected from Table 3.

40. The method of claim 35, wherein the one or more proteins are selected from Table3. A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F.

41. The method of claims 38 or 39, wherein the one or more proteins comprise at least the proteins of Table 3.G.

42. A method of evaluating a subject for SCLC, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; thereby evaluating the subject for cancer.

43. The method of claim 42, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having SCLC.

44. The method of claim 42 or 43, further comprising administering a treatment to the subject.

45. A method of treating SCLC in a subject, comprising(a) acquiring results from the method of claims 42 or 43; and(b) administering a treatment to the subject.

46. The method of claim 45, wherein the treatment is responsive to the results acquired in (a).

47. The method of claim 45 or 46, wherein (a) comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has SCLC.

48. A method of treating SCLC in a subject, the method comprising:(a) acquiring results from an evaluation of the subject that determined the subject has SCLC;(b) administering a treatment to the subject, wherein the evaluation comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has SCLC.

49. The method of any one of claims 45-48, wherein the results in (a) are acquired from a third party.

50. A method of detecting SCLC in a subject, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.

51. The method of claim 50, further comprising administering a treatment to the subject.

52. A method of treating SCLC in a subject, comprising(a) acquiring results from the method of claim 39; and(b) administering a treatment to the subject.

53. The method of claim 52, wherein the treatment is responsive to the results acquired in (a).

54. A method of treating SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected; and administering a treatment to the subject when SCLC is detected.

55. A method of treating SCLC in a subject in whom SCLC was detected, the method comprising administering a treatment for SCLC to the subject, wherein SCLC was detected in the subject by a method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that SCLC is detected.

56. The method of claim 55, wherein the method of detecting SCLC was performed by a third party.

57. The method of any one of claims 42-56, wherein the NSCLC is early-stage.

58. The method of any one of claims 42-56, wherein the NSCLC is late-stage.

59. The method of any one of claims 42-56, wherein the subject is asymptomatic ofNSCLC.

60. The method of any one of claims 42-56, wherein the subject is undergoing a screen for SCLC.

61. The method of any one of claims 42-56, wherein the subject is symptomatic of SCLC.

62. A method of evaluating a treatment for SCLC in a subject, the method comprising:(a) administering a treatment for SCLC, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; thereby evaluating the treatment.

63. A method of evaluating the efficacy of a treatment for SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 4, or from Table 5, or from Table 6; thereby evaluating the efficacy of the treatment.

64. A method of treating SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.

65. A method of adjusting a treatment for SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject,(b) determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 4, or from Table 5, or from Table 6, and(c) administering an adjusted treatment to the subject when it is determined that the adjusted treatment is necessary.

66. A method of treating SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.

67. The method of claim 66, further comprising administering an adjusted treatment when it is determined that the adjusted treatment is necessary.

68. A method of monitoring for SCLC recurrence in a subject, comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the SCLC is recurring, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.

69. A method of treating SCLC in a subject, the method comprising(a) administering a treatment for SCLC to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 4, or from Table 5, or from Table 6.

70. The method of claim 68 or 69, further comprising administering a second treatment when it is determined that the cancer is recurring.

71. The method of any one of claims 62-70, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having SCLC.

72. The method of any one of claims 42-71, wherein the one or more proteins are selected from Table 4.

73. The method of claim 72, wherein the one or more proteins are selected from Table 4. A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F.

74. The method of any one of claims 42-72, wherein the one or more proteins comprise at least the proteins of Table 4.G.

75. The method of any one of claims 42-71, wherein the subject is female.

76. The method of claim 75, wherein the one or more proteins are selected from Table 5.

77. The method of claim 76, wherein the one or more proteins are selected from Table5. A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F.

78. The method of claims 75 or 76, wherein the one or more proteins comprise at least the proteins of Table 5.G.

79. The method of any one of claims 42-71, wherein the subject is male.

80. The method of claim 79, wherein the one or more proteins are selected from Table 6.

81. The method of claim 80, wherein the one or more proteins are selected from Table6. A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F.

82. The method of claims 79 or 80, wherein the one or more proteins comprise at least the proteins of Table 6.G.

83. A method of evaluating a subject for lung cancer that is either NSCLC or SCLC, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; thereby evaluating the subject for cancer.

84. The method of claim 83, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having lung cancer.

85. The method of claim 83 or 84, further comprising administering a treatment to the subject.

86. A method of treating lung cancer that is either NSCLC or SCLC in a subject, comprising(a) acquiring results from the method of claims 61 or 62; and(b) administering a treatment to the subject.

87. The method of claim 86, wherein the treatment is responsive to the results acquired in (a).

88. The method of claim 86 or 87, wherein (a) comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has lung cancer.

89. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising:(a) acquiring results from an evaluation of the subject that determined the subject has lung cancer;(b) administering a treatment to the subject, wherein the evaluation comprises:(i) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and(ii) applying a classifier to the concentration of the one or more proteins to identify whether the subject has lung cancer.

90. The method of any one of claims 86-89, wherein the results in (a) are acquired from a third party.

91. A method of detecting lung cancer that is either NSCLC or SCLC in a subject, the method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; and applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.

92. The method of claim 91, further comprising administering a treatment to the subject.

93. A method of treating lung cancer that is either NSCLC or SCLC in a subject, comprising(a) acquiring results from the method of claim 91; and(b) administering a treatment to the subject.

94. The method of claim 93, wherein the treatment is responsive to the results acquired in (a).

95. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected; and administering a treatment to the subject when lung cancer is detected.

96. A method of treating lung cancer that is either NSCLC or SCLC in a subject in whom lung cancer was detected, the method comprising administering a treatment for lung cancer to the subject, wherein lung cancer was detected in the subject by a method comprising: determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; andapplying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative that lung cancer is detected.

97. The method of claim 96, wherein the method of detecting lung cancer was performed by a third party.

98. The method of any one of claims 83-97, wherein the lung cancer is early-stage.

99. The method of any one of claims 83-97, wherein the lung cancer is late-stage.

100. The method of any one of claims 83-97, wherein the subject is asymptomatic of lung cancer.

101. The method of any one of claims 83-97, wherein the subject is undergoing a screen for lung cancer.

102. The method of any one of claims 83-97, wherein the subject is symptomatic of lung cancer.

103. A method of evaluating a treatment for lung cancer that is either NSCLC or SCLC in a subject, the method comprising:(a) administering a treatment for lung cancer, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9; thereby evaluating the treatment.

104. A method of evaluating the efficacy of a treatment for lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins selected from Table 7, or from Table 8, or from Table 9;thereby evaluating the efficacy of the treatment.

105. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate the efficacy of the treatment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.

106. A method of adjusting a treatment for lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject,(b) determining in a biological sample from the subject a concentration of one or more proteins, wherein the one or more proteins are selected Table 7, or from Table 8, or from Table 9, and(c) administering an adjusted treatment to the subject when it is determined that the adjusted treatment is necessary.

107. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the treatment requires adjustment, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.

108. The method of claim 107, further comprising administering an adjusted treatment when it is determined that the adjusted treatment is necessary.

109. A method of monitoring for lung cancer that is either NSCLC or SCLC recurrence in a subject, comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether the lung cancer is recurring, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.

110. A method of treating lung cancer that is either NSCLC or SCLC in a subject, the method comprising(a) administering a treatment for lung cancer to the subject, and(b) determining in a biological sample from the subject a concentration of one or more proteins to evaluate whether cancer is recurring, wherein the one or more proteins are selected from Table 7, or from Table 8, or from Table 9.

111. The method of claim 109 or 110, further comprising administering a second treatment when it is determined that the cancer is recurring.

112. The method of any one of claims 103-111, further comprising applying a classifier to the concentration of the one or more proteins that identifies whether the concentration of the one or more proteins is indicative of the subject having lung cancer.

113. The method of any one of claims 83-112, wherein the one or more proteins are selected from Table 4.

114. The method of claim 113, wherein the one or more proteins are selected from Table 4. A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F.

115. The method of any one of claims 83-113, wherein the one or more proteins comprise at least the proteins of Table 4.G.

116. The method of any one of claims 83-112, wherein the subject is female.

117. The method of claim 116, wherein the one or more proteins are selected from Table 5.

118. The method of claim 117, wherein the one or more proteins are selected from Table5. A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F.

119. The method of claims 116 or 117, wherein the one or more proteins comprise at least the proteins of Table 5.G.

120. The method of any one of claims 83-112, wherein the subject is male.

121. The method of claim 120, wherein the one or more proteins are selected from Table 6.

122. The method of claim 121, wherein the one or more proteins are selected from Table6. A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F.

123. The method of claims 120 or 121, wherein the one or more proteins comprise at least the proteins of Table 6.G.

124. The method of any one of claims 1-123, wherein the biological sample is selected from a plasma sample, serum sample, saliva sample, CSF sample, sweat sample, urine sample, or tear sample.

125. The method of claim 124, wherein the biological sample is a plasma sample.

126. The method of any one of claims 1-125, further comprising collecting the biological sample from the subject.

127. The method of claim 126, wherein the collection of the biological sample is performed in the home of the subject.

128. The method of claim 127, wherein the collection of the biological sample is performed in a medical facility.

129. The method of any one of claims 1-128, wherein the determination of the concentration of the one or more proteins is performed in the home of the subject.

130. The method of any one of claims 1-128, wherein the determination of the concentration of the one or more proteins is performed in a medical facility.

131. The method of any one of claims 1-130, wherein the number of proteins for which the concentration is determined is sufficient to achieve an AUC of a ROC curve of at least about 0.6.

132. The method of claim 131, wherein the number of proteins for which the concentration is determined is sufficient to achieve an AUC of a ROC curve of at least about 0.7.

133. The method of claim 132, wherein the number of proteins for which the concentration is determined is sufficient to achieve an AUC of a ROC curve of at least about 0.8.

134. The method of any one of claims 1-133, wherein the concentration of the two or more proteins is determined by one or more assays.

135. The method of any one of claims 21-30, 62-71, or 103-112, wherein the administration of the treatment in (a) is performed by a third party.

136. The method of any one of claims 21-30, 62-71, or 103-112, wherein the determination in the biological sample from the subject a concentration of one or more proteins in (b) is performed by a third party.

137. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 1.

138. The method of claim 137, wherein the one or more proteins are selected from Table l.A, Table l.B, Table l.C, Table l.D, Table l.E, or Table l.F.

139. The method of claim 137, wherein the one or more proteins are at least the proteins of Table EG.

140. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 2.

141. The method of claim 140, wherein the one or more proteins are selected from Table2. A, Table 2.B, Table 2.C, Table 2.D, Table 2.E, or Table 2.F.

142. The method of claim 140, wherein the one or more proteins are at least the proteins of Table 2.G.

143. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 3.

144. The method of claim 143, wherein the one or more proteins are selected from Table3. A, Table 3.B, Table 3.C, Table 3.D, Table 3.E, or Table 3.F.

145. The method of claim 143, wherein the one or more proteins are at least the proteins of Table 3. G.

146. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 4.

147. The method of claim 146, wherein the one or more proteins are selected from Table4. A, Table 4.B, Table 4.C, Table 4.D, Table 4.E, or Table 4.F.

148. The method of claim 146, wherein the one or more proteins are at least the proteins of Table 4.G.

149. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 5.

150. The method of claim 149, wherein the one or more proteins are selected from Table 5.A, Table 5.B, Table 5.C, Table 5.D, Table 5.E, or Table 5.F.

151. The method of claim 149, wherein the one or more proteins are at least the proteins of Table 5.G.

152. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 6.

153. The method of claim 152, wherein the one or more proteins are selected from Table6. A, Table 6.B, Table 6.C, Table 6.D, Table 6.E, or Table 6.F.

154. The method of claim 152, wherein the one or more proteins are at least the proteins of Table 6.G.

155. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 7.

156. The method of claim 155, wherein the one or more proteins are selected from Table7. A, Table 7.B, Table 7.C, Table 7.D, Table 7.E, or Table 7.F.

157. The method of claim 155, wherein the one or more proteins are at least the proteins of Table 7.G.

158. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 8.

159. The method of claim 158, wherein the one or more proteins are selected from Table8. A, Table 8.B, Table 8.C, Table 8.D, Table 8.E, or Table 8.F.

160. The method of claim 158, wherein the one or more proteins are at least the proteins of Table 8.G.

161. A method of measuring amounts of proteins in a subject, the method comprising determining individual amounts of one or more proteins selected from Table 9.

162. The method of claim 161, wherein the one or more proteins are selected from Table 9. A, Table 9.B, Table 9.C, Table 9.D, Table 9.E, or Table 9.F.

163. The method of claim 161, wherein the one or more proteins are at least the proteins of Table 9.G.

164. The method of any one of claims 1-163, wherein two or more proteins are selected.

165. The method of any one of claims 1-164, wherein three or more proteins are selected.

166. The method of any one of claims 1-65, wherein five or more proteins are selected.

167. The method of any one of claims 1-66, wherein ten or more proteins are selected.

168. The method of any one of claims 1-167, wherein 20 or more proteins are selected.

169. The method of any one of claims 1-168, wherein 30 or more proteins are selected.

170. The method of any one of claims 1-169, wherein all proteins are selected.

171. The method of any one of claims 1-163, wherein no more than about 30 proteins are selected.

172. The method of any one of claims 1-163, wherein no more than about 20 proteins are selected.

173. The method of any one of claims 1-163, wherein no more than about ten proteins are selected.

174. The method of any one of claims 1-163, wherein no more than about five proteins are selected.

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