(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder

Abstract

(Pro)renin receptor (PRR) is being investigated in several malignancies as it activates pathogenic pathways that contribute to cell proliferation, immunosuppressive microenvironments, and acquisition of aggressive neoplastic phenotypes. Its implication in urothelial cancer (UC) has not been evaluated so far. We retrospectively evaluate the prognostic role of PRR expression in a series of patients with invasive UC treated with radical cystectomy and other clinical and histopathological parameters including p53, markers of immune-checkpoint inhibition, and basal and luminal phenotypes evaluated by tissue microarray. Cox regression analyses using stepwise selection evaluated candidate prognostic factors and disease-specific survival. PRR was expressed in 77.3% of the primary tumors and in 70% of positive lymph nodes. PRR expression correlated with age (p = 0.006) and was associated with lower preoperatively hemoglobin levels. No other statistical association was evidenced with clinical and pathological variables (gender, ASA score, Charlson comorbidity index, grade, pT, pN) or immunohistochemical expressions evaluated (CK20, GA-TA3, CK5/6, CD44, PD-L1, PD-1, B7-H3, VISTA, and p53). PRR expression in primary tumors was associated with worse survival (log-rank, p = 0.008). Cox regression revealed that PRR expression (HR 1.85, 95% CI 1.22–2.8), pT (HR 7.02, 95% CI 2.68–18.39), pN (HR 2.3, 95% CI 1.27–4.19), and p53 expression (HR 1.95, 95% CI 1.1–3.45) were independent prognostic factors in this series. In conclusion, we describe PRR protein and its prognostic role in invasive UC for the first time. Likely mechanisms involved are MAPK/ERK activation, Wnt/β-catenin signaling, and v-ATPAse function.

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

“…It is still surprising that despite decades of intensive research the optimal tissue markers for urothelial cancer remains undetermined. Recent developments regarding basal/luminal phenotype markers are consolidating to predict disease prognosis, but other new immunohistochemical evaluations such as fibroblast activating protein (FAP) or pro-renin receptor (PRR) are also newly discovered [25,26].…”