MUC16 Alternation is a Potential Biomarker for Prognosis in Patients with Gastric Cancer Receiving Immunotherapy

Abstract

Background: Immune checkpoint inhibitors (ICIs) have recently attracted much attention for the treatment of gastric cancer. However, the response rate of patients without selective treatment is low. Therefore, screening for the predictors of ICIs efficacy prior to treatment is the key to providing the ideal treatment. Cell surface associated Mucin 16 (MUC16) is significantly related to the occurrence and progress of various malignant tumors. Therefore, the relationship between MUC16 and the efficacy of ICIs, as well as its potential mechanism, require further study. Methods: We began by collecting a gastric cancer data set from a public database, and the immunotherapy cohort that we chose was selected from published studies. We analyzed the influence of MUC16 mutation on clinical prognosis, gene mutation frequency, and the immune microenvironment. Gene Set Enrichment Analysis (GSEA) was used to evaluate significant up-regulation and down-regulation in response pathways. We used the drug data from the Genomics of Drug Sensitivity in Cancer (GDSC) database to analyze the influence of MUC16 mutation on drug sensitivity. Results: Univariate and multivariate Cox regression analysis and logistic regression analysis show that the presence of MUC16 mutation can result in a better prognosis for patients and high efficacy of immunotherapy, and as such can be used as an independent factor to predict the efficacy of ICIs. The analysis results of immunogenicity and the immune microenvironment showed that MUC16 mutation causes a higher tumor mutation load and new antigen load, higher levels of activated immune cells, and significantly up-regulated immune response-related pathways. Conclusions: MUC16 mutation can be used as an independent predictor of the curative effect of ICIs treatment in patients with gastric cancer, and it is related to greater immunotherapy efficacy, higher immunogenicity, and a significantly improved immune microenvironment.