Cancer Antigen 125 Expression Enhances the Gemcitabine/Cisplatin-Resistant Tumor Microenvironment in Bladder Cancer

Cancer antigen 125 (CA125) is one of the mucin family proteins and is a serum tumor marker for various tumors, such as ovarian cancer, endometrial cancer, pancreatic cancer, and bladder cancer. CA125 is used to distinguish between benign and malignant tumors, monitor the response to chemotherapy, and detect relapse after initial treatment. Recently, CA125 was reported to be involved in chemoresistance through the physical characteristics of mucin or by modifying the immune tumor-microenvironment. However, the relationship between CA125 expression and chemoresistance in bladder cancer is still unclear. In this study, the clinicopathologic features of bladder cancer with CA125 expression and the status of the tumor-microenvironment related to gemcitabine/cisplatin resistance were investigated using publicly available data sets (Cancer Genome Atlas Expression, GSE169455 data set) from the cBioPortal website, the National Center for Biotechnology Information website, and an in-house case collection of bladder cancer. The cases with CA125 expression had poorer disease-free and overall survival rates than those without CA125 expression. A mucinous area surrounding cancer cells was frequently detected in cases with CA125 expression (81%; 13/16 cases). CA125 expression was also related to the immunosuppressive tumor-microenvironment through the infiltration of immunosuppressive immune cells, such as regulatory T cells and M2 macrophages. These results suggest that the status of tumor-microenvironment associated with CA125 is involved in gemcitabine/cisplatin resistance in bladder cancer.