INHBA overexpression indicates poor prognosis in urothelial carcinoma of urinary bladder and upper tract.

Abstract

Urothelial carcinoma (UC) originating from the bladder (UBUC) and upper urinary tract (UTUC) is the most common type of urinary tract tumor. While its pathogenesis remains obscured. Computerizing a published transcriptomic database of UBUC (GSE31684), we identified Inhibin, Beta A (INHBA) as the most significant upregulated gene associated with tumor progression among those associated with growth factor activity (GO:0008083). We therefore analyzed the clinicopathological significance of INHBA expression in UC. QuantiGene assay was used to detect INHBA transcript level in 36 UTUCs and 30 UBUCs. Immunohistochemistry evaluated by H-score was used to determine INHBA protein expression in 340 UTUCs and 296 UBUCs. INHBA expression was correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). Increments of INHBA transcript level was associated with higher pT status in both UTUC and UBUC. INHBA protein overexpression was significantly associated with advanced clinicopathological features in both groups of UC. INHBA overexpression significantly implied inferior DSS (UTUC, P = 0.002; UBUC, P = 0.005) and MeFS (UTUC and UBUC, both P < 0.001) in multivariate analysis. INHBA overexpression implies adverse clinical outcomes for UC, justifying it is a potential prognostic biomarker and a novel therapeutic target in UC.