Novel DNA damage repair signature for immunotherapy and a proposed molecular subtyping scheme in gastric cancer

Abstract The DNA damage repair (DDR) mechanisms is closely related to the occurrence and progression of cancer cells. The diversity and complexity of DNA repair mechanisms also affect the tumor immune microenvironment. In this study, we analyzed gastric cancer gene-related data to select 19 DDR genes associated with prognosis.Through LASSO and multivariate Cox regression analysis, we obtained a prognostic model for gastric cancer based on two genes (CHAF1A, PER1) and validated it by qPCR with 30 pairs of GC samples. Moreover, small-molecule compounds targeting the antitumor effects of predictive genes were identified through molecular docking. Based on this model, we compared the immune characteristics of the two groups of patients and the differences in tumor immune microenvironment (TME), and further predicted the outcome and prognosis of immunotherapy. Additionally, we used consensus clustering and k-means methods to further identify molecular subtypes of patients, and compared the immune characteristics of the two DDR subtypes and predicted the drug sensitivity of the two subtypes of patients to standard clinical chemotherapy drugs.