Abstract
(1) Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin–angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future.
Highlights
Renal cell carcinoma (RCC) is one of the most common malignancies in Western Countries [1,2,3]
Clear-cell renal cell carcinoma (CCRCC) is the most aggressive of the RCCs; 30% of patients are metastatic at diagnosis and another 30% of patients with localized disease eventually progress to metastatic disease [5]
A close correlation between some specific genomic signatures and clinical aggressiveness has been detected in recent studies [7], but an easier identification of changes linked to tumour behaviour and clinical outcome is necessary to reach an efficient improvement in the management of CCRCC patients [8]
Summary
Renal cell carcinoma (RCC) is one of the most common malignancies in Western Countries [1,2,3]. The mechanism of action of these drugs is based on the inhibition of the ACE/Ang-II/AT1R axis, which induce cell proliferation, fibrosis and inflammation [9,12] These phenomena are part of neoplastic processes and, the study of RAS and the potential of RAS-targeting therapies has received considerable attention in research into renal cancer [9,11]. PRR is considered to function as a hinge molecule between the Wnt receptor and the V-ATPase that mediates Wnt receptor internalization and the subsequent Wnt/β–catenin signaling [12,21] These RAS-dependent and -independent signalling pathways contribute to cancer initiation, so it was expected that PRR expression could be altered in tumour tissues [21]. Since CCRCC is the most frequent RCC [5], we analysed the association between PRR and tumour progression and its impact on the prognosis of CCRCC patients
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