Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients
| Autor: | Gorka Larrinaga, Maider Beitia, Miguel Unda, Charles H. Lawrie, José I. López, Itxaro Perez, Jon Danel Solano-Iturri, Julio Calvete-Candenas, Peio Errarte, Lorea Manterola |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine system inhibitors Colorectal cancer Angiogenesis Peptide Hormones lcsh:Medicine Kaplan-Meier Estimate Immunostaining medicine.disease_cause Biochemistry Renin-Angiotensin System converting enzyme 0302 clinical medicine Renal cell carcinoma Medicine and Health Sciences lcsh:Science Aged 80 and over Staining Kidney Multidisciplinary aminopeptidase Papillary renal cell carcinomas Proteases Middle Aged Prognosis peptidase activity Immunohistochemistry Enzymes Bioassays and Physiological Analysis medicine.anatomical_structure Oncology Nephrology Renal Cancer 030220 oncology & carcinogenesis Female Neprilysin Angiotensin-Converting Enzyme 2 Anatomy Research Article Adult Histology Peptidyl-Dipeptidase A Glutamyl Aminopeptidase Research and Analysis Methods Carcinomas survival 03 medical and health sciences medicine Humans Carcinoma Renal Cell endopeptidase Aged Proportional Hazards Models Renal Analysis therapy business.industry lcsh:R Renal Cell Carcinoma colorectal-cancer Cancers and Neoplasms Biology and Life Sciences Proteins Kidneys Renal System medicine.disease Hormones Genitourinary Tract Tumors Clear cell renal cell carcinoma 030104 developmental biology Tissue Array Analysis Specimen Preparation and Treatment Multivariate Analysis Enzymology Cancer research lcsh:Q progression business Carcinogenesis serum |
| Zdroj: | PLoS ONE, Vol 12, Iss 8, p e0181711 (2017) Addi. Archivo Digital para la Docencia y la Investigación instname PLoS ONE |
| Popis: | The 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. 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). 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) |
| Databáze: | OpenAIRE |
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