CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder

Aims: Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort. Methods and results: Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and diseasespecific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis. Conclusions: CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.