Ectonucleotidases CD39 and CD73 expression levels are independent and inverse predictors of survival in muscle-invasive bladder cancer

Abstract

Bladder cancer is one of the leading causes of cancer-related mortality worldwide. Long-term survival is particularly poor in patients with muscle-invasive bladder cancer (MIBC). Modulation of purinergic signaling through the ectonucleotidases CD39 and CD73 has emerged as a promising therapeutic strategy in cancer medicine. Altered expression patterns of these molecules have been linked to prognosis in various malignancies. In this study, we assessed the value of CD39 and CD73 expression as prognostic markers and potential therapeutic targets in MIBC. CD39 and CD73 expression was determined by immunohistochemistry using tissue microarrays from 180 patients with MIBC. Associations between tumoral and stromal expression and clinicopathological variables, including overall survival (OS), tumor-specific survival (TSS) and disease-free survival (DFS), were analyzed. Tumor cells did not express CD39. High stromal CD39 expression was significantly associated with a lower T category and UICC stage as well as prolonged median OS, TSS, and DFS. High CD73 expression by tumor cells was significantly associated with poorer OS and TSS. Stromal CD73 expression was not significantly correlated with survival outcomes. Our findings indicate distinct and compartment-specific roles for CD39 and CD73 in MIBC. They suggest that high CD73 expression in tumor cells and low CD39 expression in stromal cells are negative prognostic indicators and potential therapeutic targets in MIBC.