Gene combination and application thereof in preparation of reagent for predicting prognosis of patient treated by immune checkpoint inhibitor

A gene combination and gene technology, applied in the field of biomedicine, can solve the problems of differences in TMB, difficult to achieve, affecting the accuracy of TMB, etc., and achieve the effect of high efficiency, easy clinical promotion, and economic burden reduction.

Active Publication Date: 2019-09-13
WUHAN UNIV
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AI Technical Summary

Problems solved by technology

In view of the high cost of whole exome sequencing, targeted gene sequencing is mainly used at present. Although studies have shown that the TMB calculated by targeted gene sequencing based on a large gene combination is significantly correlated with the TMB calculated based on WES, different sizes of sequencing combinations will affect TMB accuracy
At present, the gene sequencing combination used t...

Method used

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  • Gene combination and application thereof in preparation of reagent for predicting prognosis of patient treated by immune checkpoint inhibitor
  • Gene combination and application thereof in preparation of reagent for predicting prognosis of patient treated by immune checkpoint inhibitor

Examples

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Embodiment 1

[0031] [Example 1] TMS55 analysis of targeted gene sequencing data of 1661 patients receiving immune check inhibitors

[0032]Reference 4 discloses targeted gene sequencing data of 1661 tumor samples from patients receiving immunocheck inhibitor therapy, and the sequenced gene combination is MSK-IMPACT. Tumor samples from 1,661 patients included 215 cases of bladder cancer, 44 cases of breast cancer, 110 cases of colorectal cancer, 126 cases of esophageal and gastric cancer, 117 cases of glioma, 139 cases of head and neck cancer, 350 cases of non-small cell lung cancer, and 321 cases of melanoma , 151 cases of kidney cancer and 88 cases of tumors with unknown primary sites. Each sample received targeted sequencing of no less than 300 gene combinations. The data disclosed in reference 4 provides the necessary survival data and TMB data. In the prognostic analysis, the cutoff value of TMB level is divided according to the percentage in each tumor type (top10%, top10-20% and bot...

Embodiment 2

[0040] [Example 2] Comparison of the results of TMS55 and TMB for 1661 patients receiving immune check inhibitors

[0041] The present invention calculates the TMS and TMB of 1661 patients receiving immune check inhibitors by using the targeted gene sequencing data of tumor samples of patients receiving immune check inhibitor treatment disclosed in reference 4, and the results show that TMS has a significant correlation with TMB ( figure 1 ). Total TMS including all sequenced genes had a very high correlation with TMB (R=0.98, P-16 , figure 1 A). In the identification of positive and negative mutation genes, the present invention identifies 55 positive mutation genes, and calculates TMS55, that is, the number of non-synonymous mutation genes among the 55 genes. Therefore, the minimum value of TMS55 is 0, the maximum value is 55, and it is an integer. Its TMS55 also had a high correlation with TMB (R=0.91, P-16 , figure 1 B). These results showed that although TMS55 elimin...

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Abstract

The invention provides a gene combination and application thereof in preparation of a reagent for predicting prognosis of a patient treated with an immune checkpoint inhibitor. Based on the combination of 55 genes, the invention develops a tumor mutation score TMS32055 method through the gene combination, and TMS is defined as the number of genes containing non-synonymous mutations in a specific gene combination. TMS 55 is divided into 3 groups: TMS 55 is equal to 0, TMS 55 is greater than or equal to 1 and is less than or equal to 5, and TMS 55 is greater than 5. Compared with a group that TMS 55 is equal to 0, the patients of groups that TMS 55 is greater than or equal to 1 and is less than or equal to 5 and TMS 55 is greater than 5 have better prognosis and longer overall survival time.The TMS55 based on the 55-gene combination has higher prediction efficiency than TMB in predicting the overall survival after immunotherapy, and has uniform cutoff value. Therefore, the TMS55 can beused for predicting the prognosis of patients receiving immune checkpoint inhibition treatment, and is easier to popularize and apply in clinical practice.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a gene combination and its application in the preparation of reagents for predicting the prognosis of patients treated with immune checkpoint inhibitors. Background technique [0002] Immunotherapy is a current research hotspot. The application of immune checkpoint inhibitors has opened up a new era of tumor treatment, but the lack of efficient biomarkers largely affects its efficacy and application. Tumor Mutation Burden (TMB) refers to the total number of somatic non-synonymous gene mutations detected per million bases, including coding errors, base substitutions, gene insertion or deletion errors, etc. Mutations in somatic cells are finally expressed at the protein level through transcription and translation. Mutations produce new antigens such as new protein fragments or polypeptide fragments, which are recognized by the autoimmune system as non-self antigens, activate T ce...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/118C12Q2600/156
Inventor 李源陶卫平伍龙
Owner WUHAN UNIV
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