Comprehensive investigation of CPSF3's role in the progression of bladder cancer.

829 Background: Bladder cancer (BC) is a global health issue, with a significant number of new cases diagnosed annually. Despite advances in treatment, many patients experience recurrence or progression, emphasizing the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance and biological function of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. Methods: We analyzed CPSF3 expression using The Cancer Genome Atlas (TCGA) data and immunohistochemistry (IHC) on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was constructed to predict overall survival (OS) and disease-free survival (DFS). In vitro experiments were conducted to assess the effect of CPSF3 knockdown on BC cell proliferation, colony formation and cell cycle distribution. Bioinformatics analyses, including Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis, were performed to explore potential mechanisms. Results: High CPSF3 expression was significantly associated with poor OS and DFS in TCGA and our cohort. The nomogram incorporating CPSF3 showed superior predictive performance compared to traditional models. Downregulation of CPSF3 inhibited BC cell proliferation, colony formation and transition from G1 phase to S phase. GSEA revealed enrichment of oncogentic pathways in CPSF3 high-expression phenotype. CPSF3 expression was correlated with immune cell infiltration and expression of immune checkpoints in the tumor microenvironment. Conclusions: Our study demonstrates that CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression. The nomogram incorporating CPSF3 expression provides an improved tool for predicting BC patient outcomes. These findings suggest that CPSF3 could be a potential therapeutic target for BC treatment.