Overexpression of replication protein A3 is associated with unfavorable outcome in bladder urothelial carcinoma

Abstract

Purpose: The replication protein A3 (RPA3) is a subunit of the RPA protein complex, which plays an essential role in multiple processes of DNA metabolism. However, the involvement of RPA3 bladder urothelial carcinoma (UC) prognosis has not yet been elucidated. The aim of our study is to investigate the prognostic role of RPA3 expression in patients with bladder UC. Materials and Methods: Bladder UC tissue specimens from 155 consecutively treated patients who underwent surgery between 2013 and 2018 were evaluated. The RPA3 expression was determined by immunohistochemistry, Western blot, and correlated with clinicopathological parameters. The prognostic significance of RPA3 expression was explored using the univariate and multivariate survival analysis of 155 patients who were followed. Results: A total of 155 tissue specimens 'of patients' who were regularly followed with the mean 39.6 months (from 4 to 71 months). The expression of RPA3 was significantly associated with tumor grade (P = 0.031) and stage (P = 0.021), as well as tumor size (P = 0.034). In univariate analysis, RPA3 overexpression showed an unfavorable influence on recurrence-free survival with statistical significance (P < 0.01). TNM stage and grade also showed strong statistical relation with adverse recurrence-free survival (P < 0.01, P = 0.030). Multivariate analysis revealed that grade, stage, and RPA3 reactivity (P = 0.025, P < 0.01, P = 0.016) were identified as independent prognostic factors for recurrence-free survival in patients with bladder UC. Conclusions: These results of this study proved that elevated expression of RPA3 was associated with worse clinical outcome in bladder UC patients. This finding suggested that RPA3 served as a potential prognostic biomarker, which could be useful to predict cancer evolution and may represent a novel therapeutic target for the intervention of bladder UC patients.