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

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...

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 to detect TMB contains more and more genes, and the cost is getting higher and higher. At the same time, the calculated TMB is different, and it is more difficult to achieve a unified cutoff value to guide clinical practice.

[0005] In summary, since the calculation of TMB includes negative mutations, it greatly affects the efficacy of TMB as a marker related to immunotherapy, and lacks a unified cutoff value

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