The incidence and mortality rates of endometrial cancer are increasing during recent years. CA125 (gene symbol MUC16) is a well-known diagnostic and prognostic serum marker of endometrial cancer. High serum CA125 level is associated with poor prognosis. MUC16 is one of the most frequently mutated genes in endometrial cancer. However, the potential relationship and underlying mechanism between MUC16 mutations and endometrial cancer patients' prognosis and disease progression remain unclear. In present study, we analyzed the whole exome sequencing data, RNA sequencing data and patients' clinical information in TCGA database and demonstrated that MUC16 mutational status was an independent prognostic factor for endometrial cancer patients. Patients with somatic MUC16 mutations had a prolonged overall survival time. MUC16 mutations promoted patients' antitumor immune responses. Cytotoxic immune cells mediated pathways were enriched in endometrial cancer samples with MUC16 mutations. Elevation of two pathways, NO2-dependent IL 12 pathway in NK cells and T cytotoxic cell surface molecules, significantly correlated with a higher rate of MUC16 mutations and a significantly favorable patients' prognosis. An increased level of cytotoxic T lymphocytes, not NK cells, infiltration was observed in the tumor microenvironment of patients with MUC16 mutations. High expression of molecular markers of T cells and CD8+ T cells associated with a higher rate of MUC16 mutations and a better patients' prognosis. These findings may provide deeper insight into potential endometrial cancer immunotherapy approaches.
Keywords: CA125; MUC16; antitumor immunity; cytotoxic T lymphocytes; endometrial cancer; mutation.