(Pro)renin Receptor Expression Increases throughout the Colorectal Adenoma—Adenocarcinoma Sequence and It Is Associated with Worse Colorectal Cancer Prognosis

Abstract

(Pro)renin receptor (PRR) is a protein that takes part in several signaling pathways such as Renin Angiotensin System and Wnt signalling. Its biological role has recently been related to cancer progression and in this study, we investigated its relevance in colorectal cancer (CRC). To that end, we analysed the immunohistochemical expression of PRR in adenomatous polyps and CRCs from the same patients (n = 42), and in primary tumours and nodal and liver metastases from advanced CRC patients (n = 294). In addition, the soluble fraction of PRR was measured by ELISA in plasma samples from 161 CRC patients. The results showed that PRR expression was gradually augmented along the uninvolved mucosa–adenoma–adenocarcinoma sequence. Besides, the stronger expression of PRR in primary tumours was markedly associated with local tumour extent and the onset of metastases. Moreover, PRR expression in both primary and distant metastases was associated with worse 5- and 10-year survival of CRC patients. Plasmatic PRR levels did not change with respect to controls and were not associated with CRC aggressiveness. These results suggest a key role of PRR in the development and progression of CRC and a potential use of this protein as a new prognostic biomarker and/or therapeutic target for this disease.

Clinical Implications of (Pro)renin Receptor (PRR) Expression in Renal Tumours

“…These results agree with studies carried out in other solid tumours, showing the potential of PRR as a biomarker of worse prognosis [21]. Furthermore, we reported recently that PRR staining was not very different in the centre and front of colorectal cancers [27], a result that was repeated in RCCs. This finding suggests that the intrinsic heterogeneity of these tumours may not affect their analysis, which is favourable for the potential use of PRR as an immunohistochemical prognostic biomarker [27].…”

“…Our data show cytoplasmic granular staining of PRR in RCCs, which could be associated with these intracellular phenomena. PRR has also been described in benign tumours, such as adrenal [46,47] and colorectal adenomas [27]. In agreement with this, our results showed that PRR was expressed in RO and with the same intensity as in ChRCC, tumours that are histogenetically related [6].…”

The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers

“…We found that higher (P) RR expression levels are more commonly observed in patients with the following characteristics: male sex, early age at onset, poorly differentiated lesions, advanced cancer stage, distant metastasis, rapid progression, lower 5-year survival rate and shorter recurrence-free survival time (Table 1). Recently, Maider et al [44] reported their latest data which are highly consistent with our previous findings. In their study, (P) RR protein levels were detected in tissues of adenomatous polyps and cancers from the same CRC patients (n = 42), as well as in tissues of primary tumors and nodal and liver metastases from advanced CRC patients (n = 294) [44].…”

“…In their study, (P) RR protein levels were detected in tissues of adenomatous polyps and cancers from the same CRC patients (n = 42), as well as in tissues of primary tumors and nodal and liver metastases from advanced CRC patients (n = 294) [44]. The results showed that (P) RR expression increases throughout the colorectal adenoma-adenocarcinoma process, moreover, (P) RR protein in both primary tumor and distant metastases is associated with worse prognosis including 5-and 10-year survival of CRC patients [44].…”

“…However, the predictive value of plasmatic s(P) RR in CRC and primary epithelial ovarian cancer (EOC) seems not that obvious. Maider et al [44] collected plasma from 161 patients with CRC followed by the measurement of s(P) RR, as a result, they found that plasmatic s(P) RR of CRC patients were at similar level to that of healthy controls and was not associated with disease progression. Additionally, Katrin et al [49] tested s(P) RR in the plasma of 197 patients with primary EOC, analyzed the potential association between plasmatic s(P) RR and clinicopathological outcome of the patients, as well as compared levels of plasmatic s(P) RR of the patients and healthy controls.…”