Comprehensive investigation identifies CPSF3 as a novel prognostic and oncogenic biomarker in bladder cancer
Background Bladder cancer (BC) remains a prevalent malignancy worldwide, with rising incidence rates each year. Despite progress in therapeutic strategies, many patients suffer recurrence or progression, emphasizing the urgent need for novel prognostic biomarkers and therapeutic targets. This research evaluated the prognostic relevance and functional role of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. Methods We analyzed CPSF3 expression using The Cancer Genome Atlas data and immunohistochemistry on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was developed based on CPSF3 expression for prediction of overall survival and disease-free survival. Immune infiltration analyses and transcriptome sequencing were performed to explore underlying biological mechanisms. In vitro and in vivo experiments were utilized to examine the results of CPSF3 silencing on bladder cancer cell growth, colony-forming ability and cell cycle transitions. Results Elevated CPSF3 expression was significantly linked to unfavorable overall survival and disease-free survival both in TCGA datasets and our cohort. The CPSF3-based nomogram outperformed conventional prognostic models. CPSF3 expression was associated with tumor-infiltrating immune cells and immune checkpoint markers. Enrichment analysis revealed CPSF3 enrichment in cell cycle-related pathways. Suppression of CPSF3 expression led to marked reductions in cell proliferation, colony formation, tumor growth in animal models and inhibited G1 to S phase progression. Conclusion CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression.  Incorporating CPSF3 into clinical prognostic models may enhance prediction of patient outcomes. CPSF3 may represent a promising therapeutic target for BC management. Overall design: human bladder cancer cell line UMUC3, CPSF3-downregulation and negative control, 3 replicates per group