OBSCN as biomarker for evaluating tumor mutation burden and anti-tumor immunity in Stomach adenocarcinoma

Background: Somatic mutations are strongly linked to cancer. Tumor mutation burden (TMB), PD-L1, and CTLA-4 are considered to be important biomarkers for selecting patients with stomach adenocarcinoma (STAD) for immune checkpoint inhibitors (ICIs) therapy. Nonetheless, whether specific gene mutations are related to prognosis, TMB, sensitivity to ICIs, and tumor-infiltrating immune cells remains unclear. Methods: : Mutation data for STAD are derived from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. Mutation data were analyzed by R software to calculate gene mutation frequency and TMB. Kaplan-Meier survival analysis and Log rank test assessed patient prognosis, and univariate and multivariate Cox regression analyses were used to identify independent risk factors. The limma package of R software was used for differential analysis. Gene set enrichment analysis (GSEA) was performed by GSEA4.1.0. TISIDB was used to validate the correlation of OBSCN mutations with immune cell infiltration in STAD TME. Results: : 16 genes both mutated in TCGA and ICGC. Although all of the 16 genes mutations are correlated to high TMB, only patients with OBSCN mutation enjoyed a better prognosis in STAD. Univariate and multivariate Cox regression analyses showed that OBSCN mutation was an independent predictor for prognosis in STAD patients. Gene Set Enrichment Analysis showed that OBSCN mutations were mainly related to peroxisome, MTORC1 signaling, and Oxidative phosphorylation. Then, compared with the OBSCN wild type (WT) group, four genes in the OBSCN mutant type (MT) group are up-regulated, and 26 genes are down-regulated. Finally, we observed higher infiltration of T cell follicular helper, NK cells, Th1 cells, Th2 cells, CD8+ T cells, central memory CD8+ T cells, and activated CD4+ T cells but lower mast cells in the OBSCN MT group. Additionally, we found STAD patients with OBSCN mutation are more sensitive to ICIs treatment and certain chemotherapy drugs such as cisplatin, 5-Fluorouracil, and Docetaxel, which are most commonly used for STAD. Conclusions: : OBSCN mutations serve as a biomarker for predicting STAD prognosis and sensitivity to ICIs and are associated with anti-tumor immunity.