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dc.contributor.authorErrarte Yarza, Peio
dc.contributor.authorBeitia San Vicente, Maider
dc.contributor.authorPérez Urzelai, Itxaro
dc.contributor.authorManterola, Lorea
dc.contributor.authorLawrie, Charles H.
dc.contributor.authorSolano Iturri, Jon Danel
dc.contributor.authorCalvete Candenas, Julio
dc.contributor.authorUnda Urzaiz, Jesús Miguel
dc.contributor.authorLópez, José I.
dc.contributor.authorLarrinaga Embeita, Gorka
dc.date.accessioned2018-06-05T12:42:34Z
dc.date.available2018-06-05T12:42:34Z
dc.date.issued2017-08-15
dc.identifier.citationPLOS ONE 12(8) : (2017) // Article ID e0181711es_ES
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/27360
dc.description.abstractThe discovery of the intrarenal renin-angiotensin system (iRAS), which regulates angiogenesis, cell differentiation and proliferation, has opened new perspectives in the knowledge of kidney carcinogenesis. In this study we analyzed the immunohistochemical expression and fluorimetric activity of four key peptidases of iRAS in tumor tissue (n = 144) and serum samples (n = 128) from patients with renal neoplasms. Neutral endopeptidase (NEP/CD10), Angiotensin-converting enzyme-2 (ACE2), and aminopeptidase A (APA) were expressed in tumor cells whilst Angiotensin-converting enzyme (ACE) was expressed in the endothelial cells of intratumor blood vessels. The expression of ACE, ACE2 and NEP/CD10 was highest in clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). The expression of these enzymes correlated with CCRCC aggressiveness. In addition, NEP/CD10 correlated with 15-year overall survival. On the other hand, APA expression was decreased in CCRCC with higher grade and stage. The loss of expression of APA independently correlated with a worse 15-year overall survival. Serum activity of ACE2, NEP/CD10 and APA was significantly higher in renal tumor patients than in healthy subjects. Serum ACE activity was lower in high grade and metastatic CCRCC patients, and NEP/CD10 activity was negatively correlated with UISS (UCLA Integrated Staging System) and SSIGN (Mayo Clinic stage, size, grade and necrosis model) scores and with overall survival of CCRCC patients. These results suggest a metabolic imbalance of iRAS in renal tumors. This finding should be taken into account in the search of new diagnostic, prognostic and therapeutic tools for this disease.es_ES
dc.description.sponsorshipThis work was partially funded by Grant SAF2013-48812-R from Ministerio de Economia y Competitividad (Spain), IT 8-11/13 from de Basque Government and UFI 11/44 from de University of the Basque Country (UPV/EHU). The current work has been developed as PhD project of PE and MB, who are recipients of a Predoctoral Fellowship from the Basque Government (Exp no PRE_2013_1_762 and PRE_2015_2_0148). This work was partially funded by Grant SAF2013-48812-R from Ministerio de Economia y Competitividad (Spain), IT 8-11/13 from de Basque Government and UFI 11/44 from de University of the Basque Country (UPV/EHU). The current work has been developed as PhD project of PE and MB, who are recipients of a Predoctoral Fellowship from the Basque Government (Exp no PRE_2013_1_762 and PRE_2015_2_0148)es_ES
dc.language.isoenges_ES
dc.publisherPublic Library Sciencees_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/SAF2013-48812-Res_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectconverting enzymees_ES
dc.subjectsystem inhibitorses_ES
dc.subjectpeptidase activityes_ES
dc.subjectcolorectal-canceres_ES
dc.subjectserumes_ES
dc.subjectaminopeptidasees_ES
dc.subjectendopeptidasees_ES
dc.subjectprogressiones_ES
dc.subjectsurvivales_ES
dc.subjecttherapyes_ES
dc.titleExpression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patientses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holder2017 Errarte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181711es_ES
dc.identifier.doi10.1371/journal.pone.0181711
dc.departamentoesEnfermeríaes_ES
dc.departamentoesMedicinaes_ES
dc.departamentoeuErizaintzaes_ES
dc.departamentoeuMedikuntzaes_ES


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2017 Errarte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as 2017 Errarte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.