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, used to distinguish between benign and malignant tumors, to monitor the response to chemotherapy, and to detect relapse after initial treatment. Recently, CA125 has been 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 clinicopathological features of bladder cancer with CA125 expression and the status of the tumor-microenvironment related to gemcitabine/cisplatin resistance, were investigated using publicly available datasets (the Cancer Genome Atlas Expression, GSE169455 dataset) from the cBioPortal website (https://www.cbioportal.org/, last access: 8/22/2022), the NCBI website (https://www.ncbi.nlm.nih.gov/, last access: 8/22/2022) and an in-house case collection of bladder cancer. The cases with CA125 expression had the poorer disease-free and overall survivals than without CA125 expression. The 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.Copyright © 2022. Published by Elsevier Inc.
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