(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder
(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 evaluate...
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MDPI AG
2021
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oai:doaj.org-article:540449eb6895475f86298f5b97ca2d372021-11-25T17:02:07Z(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder10.3390/cancers132256422072-6694https://doaj.org/article/540449eb6895475f86298f5b97ca2d372021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5642https://doaj.org/toc/2072-6694(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 (<i>p</i> = 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, <i>p</i> = 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.Gorka LarrinagaJulio Calvete-CandenasJon Danel Solano-IturriAna M. MartínAngel PueyoCaroline E. Nunes-XavierRafael PulidoJuan F. DoradoJosé I. LópezJavier C. AnguloMDPI AGarticle(pro)renin receptorurothelial carcinomaprognosisbiomarkerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5642, p 5642 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
(pro)renin receptor urothelial carcinoma prognosis biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
(pro)renin receptor urothelial carcinoma prognosis biomarker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Gorka Larrinaga Julio Calvete-Candenas Jon Danel Solano-Iturri Ana M. Martín Angel Pueyo Caroline E. Nunes-Xavier Rafael Pulido Juan F. Dorado José I. López Javier C. Angulo (Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder |
| description |
(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 (<i>p</i> = 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, <i>p</i> = 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. |
| format |
article |
| author |
Gorka Larrinaga Julio Calvete-Candenas Jon Danel Solano-Iturri Ana M. Martín Angel Pueyo Caroline E. Nunes-Xavier Rafael Pulido Juan F. Dorado José I. López Javier C. Angulo |
| author_facet |
Gorka Larrinaga Julio Calvete-Candenas Jon Danel Solano-Iturri Ana M. Martín Angel Pueyo Caroline E. Nunes-Xavier Rafael Pulido Juan F. Dorado José I. López Javier C. Angulo |
| author_sort |
Gorka Larrinaga |
| title |
(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder |
| title_short |
(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder |
| title_full |
(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder |
| title_fullStr |
(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder |
| title_full_unstemmed |
(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder |
| title_sort |
(pro)renin receptor is a novel independent prognostic marker in invasive urothelial carcinoma of the bladder |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/540449eb6895475f86298f5b97ca2d37 |
| work_keys_str_mv |
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