Use of MCM6 as a pathological prognostic marker for distant recurrence of EMZL

Abstract

The present invention relates to the application of MCM6 as a pathological prognostic marker for distant recurrence of EMZL, belonging to the field of biomedical technology. The present invention provides a method for obtaining prognostic information of extranodal marginal zone lymphoma, and predicts the prognostic information of extranodal marginal zone lymphoma by detecting the expression level of MCM6. It provides the application of a reagent for detecting MCM6 in the preparation of a prognostic diagnostic kit for extranodal marginal zone lymphoma. It provides a prognostic diagnostic kit for extranodal marginal zone lymphoma, which is used to predict whether extranodal marginal zone lymphoma has distant recurrence. The present invention screens through proteomic sequencing data to obtain the pathological prognostic biomarker MCM6 that can predict distant recurrence of EMZL patients. MCM6 is a specifically highly expressed protein for distant recurrence of EMZL, and can be used as a pathological marker for the prognosis of EMZL to guide the risk stratification and treatment decision-making of patients.

Description

Technical Field

[0001] The present invention relates to the application of MCM6 as a pathological prognostic marker for distant recurrence of EMZL, and belongs to the field of biomedical technology. Background Art

[0002] Extranodal marginal zone lymphoma (EMZL) responds well to radiotherapy and has a relatively high overall survival rate. However, distant recurrence of the disease is a key issue in the treatment of EMZL. Clinical risk factors related to distant recurrence require clinicians to make a comprehensive judgment by combining medical history, clinical symptoms and signs, and imaging features, which has a certain degree of subjectivity. Pathological features are more objective than clinical features. Currently, the proportion of Ki-67 IHC-positive cells is used clinically as a reference for poor prognosis in EMZL, but there is no relevant research to verify its effectiveness in EMZL. Therefore, EMZL lacks disease-specific prognostic pathological markers. The technical problem that urgently needs to be solved in this technical field is how to more effectively judge the prognosis of distant recurrence of EMZL. Summary of the Invention

[0003] The purpose of the present invention is to solve the technical problem of how to more effectively judge the prognosis of distant recurrence of EMZL.

[0004] To achieve the above purpose, the technical solution adopted by the present invention is to provide a method for obtaining prognostic information of extranodal marginal zone lymphoma, including predicting the prognostic information of extranodal marginal zone lymphoma by detecting the expression level of MCM6.

[0005] Preferably, the prognostic information is to predict whether extranodal marginal zone lymphoma has distant recurrence.

[0006] The present invention provides the application of a reagent for detecting MCM6 in the preparation of a prognostic diagnostic kit for extranodal marginal zone lymphoma.

[0007] Preferably, the prognosis in the above application is to predict whether extranodal marginal zone lymphoma has distant recurrence.

[0008] The present invention provides a diagnostic kit for the prognosis of extranodal marginal zone lymphoma, and the kit includes a reagent for detecting MCM6.

[0009] Preferably, the diagnostic kit is used to predict whether extranodal marginal zone lymphoma has distant recurrence.

[0010] The present invention provides a detection system, comprising a data processing device and a substance for detecting MCM6; the data processing device includes a data input module, a data recording module, a data comparison module and a conclusion output module; the data input module is configured to input the expression value of MCM6 in a sample to be tested; the data recording module is configured to store the expression value of MCM6 in the sample to be tested and a judgment threshold; the data comparison module is configured to receive the expression value of MCM6 in the sample to be tested sent by the data input module, and call the judgment threshold from the data recording module and compare it with the expression value of MCM6 in the sample to be tested; the conclusion output module is configured to receive the comparison result sent by the data comparison module, and judge the comparison result according to a predetermined judgment condition; to determine whether a patient with extranodal marginal zone lymphoma has distant recurrence.

[0011] Preferably, the substance for detecting MCM6 includes a reagent and / or an instrument for detecting the expression value of MCM6.

[0012] Compared with the prior art, the present invention has the following beneficial effects:

[0013] The present invention screens and obtains a pathological biomarker MCM6 that can predict distant recurrence in patients with EMZL through proteomic sequencing data. MCM6 is a specifically highly expressed protein in distant recurrence of EMZL, and can be used as a pathological biomarker for prognostic judgment of EMZL to guide the risk stratification and treatment decision-making of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 It is a flow chart for screening MCM6 and a scatter plot of differential gene expression;

[0015] Figure 2 It is a comparison of the relative expression levels of MCM6 and Ki-67 in the distant recurrence group by H score.

[0016] Figure 3 It is a related result graph for comparing the distant recurrence prediction abilities of MCM6 and Ki-67. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0017] To make the present invention more obvious and understandable, preferred embodiments are described in detail below in conjunction with the accompanying drawings:

[0018] As Figures 1-3 shown; the present invention provides a method for obtaining prognostic information of extranodal marginal zone lymphoma, and the method is to predict the prognostic information of extranodal marginal zone lymphoma by detecting the expression level of MCM6; the prognostic information is to predict whether extranodal marginal zone lymphoma has distant recurrence.

[0019] The present invention provides an application of a reagent for detecting MCM6 in the preparation of a prognostic diagnosis kit for extranodal marginal zone lymphoma; the prognosis in the application is to predict whether there is distant recurrence of extranodal marginal zone lymphoma.

[0020] The present invention provides a diagnostic kit for the prognosis of extranodal marginal zone lymphoma, and the kit includes a reagent for detecting MCM6; the diagnostic kit is used to predict whether there is distant recurrence of extranodal marginal zone lymphoma.

[0021] The present invention provides a detection system, which includes a data processing device and a substance for detecting MCM6; the data processing device includes a data input module, a data recording module, a data comparison module, and a conclusion output module; the data input module is configured to input the expression value of MCM6 in a sample to be tested; the data recording module is configured to store the expression value of MCM6 in the sample to be tested and a judgment threshold; the data comparison module is configured to receive the expression value of MCM6 in the sample to be tested sent by the data input module, and call the judgment threshold from the data recording module and compare it with the expression value of MCM6 in the sample to be tested; the conclusion output module is configured to receive the comparison result sent by the data comparison module, and determine the comparison result according to a predetermined determination condition; to determine whether there is distant recurrence of extranodal marginal zone lymphoma in the tested person. The substance for detecting MCM6 includes a reagent and / or an instrument for detecting the expression value of MCM6.

[0022] Example

[0023] I. Obtain the prognostic-related pathological marker MCM6 specific to EMZLs:

[0024] Select the TMT-labeled quantitative proteomic data of 27 EMZLs samples, including 6 cases of distant recurrence and 21 control patients. Through combined limma differential gene analysis and univariate Cox regression analysis, MCM6 was screened out as a protein with potential prognostic value (as Figure 1 shown). Figure 1 In Figure A of

[0025] is the flow chart for screening out MCM6, and Figure B is the scatter plot of differential gene expression.

[0026] II. Compare the distant recurrence prediction ability of MCM6 and Ki-67 as prognostic-related pathological markers specific to EMZLs:

[0027] 2.1 Comparison using H score:

[0027] Select 44 patients with paired clinical characteristics, including 11 EMZL patients with distant recurrence and 33 EMZL patients without distant recurrence, and use paraffin-embedded sections for immunohistochemical (IHC) staining to verify the prognostic value of the candidate gene, and select Ki-67 as a positive control marker. Representative images of IHC staining are shown in Figure 2Figure A. The overall H score of MCM6 in the distant recurrence group was significantly higher than that in the control group (no recurrence group) (P = 0.0006). However, there was no significant difference in the expression of Ki-67 between the two groups (distant recurrence group and no recurrence group) (as shown in Figure 2 Figure B). This indicates that MCM6 has the potential to predict distant recurrence.

[0028] 2.2 Comparison of the distant recurrence prediction ability of MCM6 and Ki-67 as specific prognostic-related pathological markers in EMZLs:

[0029] Time-dependent ROC curve analysis was used to compare the prognostic value of each candidate gene during different follow-up periods. Compared with Ki-67, MCM6 had a stronger predictive ability for distant recurrence-free survival (DRFS) (as shown in Figure 3 Figure A).

[0030] As shown in Figure 3 Figure B, the area under the ROC curve (AUC value) of MCM6 at 1 year, 3 years, and 5 years was 0.735, 0.699, and 0.757, respectively, all higher than that of Ki-67 (0.487, 0.532, 0.592).

[0031] Taking the median H score of the marker as the cut-off value, the patients were divided into two groups. The KM survival curve showed that the high expression of MCM6 was significantly correlated with shorter DRFS, while the expression of Ki-67 was not significantly correlated with DRFS (log rank p = 0.017, log rank p = 0.18; as shown in Figure 3 Figure C). This indicates that MCM6 can better predict distant recurrence compared to Ki-67.

[0032] Multivariate Cox regression analysis proved that MCM6 was an independent risk factor for distant recurrence (HR, 6.86; 95% CI: 1.32 - 35.79; P = 0.02; Table 1).

[0033] Table 1. Cox regression risk model for distant recurrence

[0034]

[0035] The above results prove that MCM6 is a specifically highly expressed protein for distant recurrence in EMZL and can be used as a pathological marker for the prognosis of EMZL.

[0036] The present invention uses proteomic sequencing data to screen the pathological prognostic biomarker MCM6 that can predict distant recurrence in EMZL patients, which can be used to guide the risk stratification and treatment decision-making of patients.

[0037] The above are only the preferred embodiments of the present invention, and do not impose any formal or substantial limitations on the present invention. It should be noted that for those of ordinary skill in the art, without departing from the premise of the present invention, several improvements and supplements can still be made, and these improvements and supplements should also be regarded as the protection scope of the present invention. Those who are familiar with the technology in this field, without departing from the spirit and scope of the present invention, any equivalent changes made by slightly modifying, decorating, and evolving the technical content disclosed above are all equivalent embodiments of the present invention; at the same time, any equivalent changes made by modifying, decorating, and evolving the above embodiments based on the substantial technology of the present invention still fall within the scope of the technical solutions of the present invention.

Claims

1. Use of a reagent for detecting MCM6 in the preparation of a prognostic diagnosis kit for extranodal marginal zone lymphoma, wherein the prognosis is to predict whether there is distant recurrence of extranodal marginal zone lymphoma.

2. A detection system, characterized in that, It includes a data processing device and a substance for detecting MCM6; the data processing device includes a data input module, a data recording module, a data comparison module, and a conclusion output module; the data input module is configured to input the expression value of MCM6 in a sample to be tested; the data recording module is configured to store the expression value of MCM6 in the sample to be tested and a judgment threshold; the data comparison module is configured to receive the expression value of MCM6 in the sample to be tested sent by the data input module, and call the judgment threshold from the data recording module and compare it with the expression value of MCM6 in the sample to be tested; the conclusion output module is configured to receive the comparison result sent by the data comparison module, and determine the comparison result according to a predetermined determination condition; to determine whether there is distant recurrence of extranodal marginal zone lymphoma in the subject to be tested.

3. The system according to claim 2, wherein: The substance for detecting MCM6 includes a reagent and / or an instrument for detecting the expression value of MCM6.

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