(Pro)renin Receptor Down-regulation Is Associated With a Higher Risk of Recurrence in Lung Adenocarcinoma.

Abstract

The (pro)renin receptor [(P)RR] plays a role not only in cardiovascular and renal diseases, but also in tumorigenesis. (P)RR contributes to the activation of the Wnt/β-catenin signaling pathway, independent of the renin-angiotensin system. Accumulating evidence has shown that (P)RR is expressed in various human cancers. However, its clinical impact in lung carcinomas remains unclear. This study aimed to clarify the associations between (P)RR expression and clinical outcomes in patients with non-small cell lung carcinoma (NSCLC). We analyzed the data of 913 patients with NSCLC who underwent resection between 1999 and 2016. Tissue microarrays were constructed and the expression of (P)RR and β-catenin was investigated using immunohistochemistry. Recurrence-free probability and overall survival were analyzed using a log-rank test and Cox proportional hazards model. In adenocarcinomas, (P)RR down-regulation correlated significantly with high-grade tumors (p=0.026) and a higher risk of recurrence in all patients (p=0.001). Among patients with (P)RR-positive tumors, the nuclear expression of β-catenin was associated with a higher risk of recurrence (p=0.001). Multivariate analysis revealed that (P)RR down-regulation was an independent predictor of disease recurrence (p=0.031). Conversely, in squamous cell carcinoma, (P)RR was not associated with patient outcomes. (P)RR down-regulation is associated with a higher risk of recurrence in lung adenocarcinomas, thereby characterizing a prognostic subset within high-grade tumors.