The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity

• DOI: 10.1186/s12885-021-07978-3
• Publication Date: 2021-03-07T14:02:42Z
• Authors: You Ge; Feiran Wei; Guoping Du; Gaoqiang Fei; Wei Li; Xiaoshan Li; Jinjin Chu; Pingmin Wei
• Keywords: ATRX; Surgical oncology

Abstract Background Genetic alterations have been proven to be the promising biomarkers for ICI response. However, sex biases in genetic often ignored field of immunotherapy, which might specially influence anticancer immunity and immunotherapy efficacy male or female patients. Here, we systematically evaluated effect somatic mutation gastric cancer (GC) patients on clinical benefit immunotherapy. Methods Genomic transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) International Consortium (ICGC). We also obtained genomic a MSKCC ICI-treated cohort cbioportal database. GC female-derived tumor profiles compared by maftools R package. Single sample gene set enrichment analysis (ssGSEA) was conducted calculate score indicators including IFN-γ signaling, cytolytic activity (CYT) antigen presenting machinery (APM). Results ATRX found mutate more frequently (FDR = 0.0108). Female with manifested significantly MSI-high subtypes, increased TMB PDL1 expression as well higher scores CYT APM. Gene (GSEA) has shown that enhance immunogenicity through affecting DNA damage repair pathways. In MSKCC, associated prolonged overall survival. When stratifying entire sex, better survival benefits than mutant (Female patients, HR MT vs WT 0.636, 95%CI 0.455–0.890, P 0.023; Male 0.929, 0.596–1.362, 0.712). Conclusions serve potential predictive biomarker favorable could applied combination other response identify who will derive greater therapy.