ArticlePloS one2017
Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review).Oncology reports · 2025Review
- Prognostic and Therapeutic Implications of Alamandine Receptor MrgD Expression in Clear Cell Renal Cell Carcinoma with Development of Metastatic Disease.Biomolecules · 2025Article
- Identification of a novel prognostic and therapeutic prediction model in clear cell renal carcinoma based on Renin-angiotensin system related genes.Frontiers in endocrinology · 2025Article
- Article
- The Expression of Alamandine Receptor MrgD in Clear Cell Renal Cell Carcinoma Is Associated with a Worse Prognosis and Unfavorable Response to Antiangiogenic Therapy.International journal of molecular sciences · 2024Article
- (Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder.Cancers · 2021Article
- Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes.Cells · 2021Review
- Potential biomarkers for the early prediction of SARS-COV-2 disease outcome.Microbial pathogenesis · 2021Review
- COVID-19 and pulmonary fibrosis: therapeutics in clinical trials, repurposing, and potential development.Archives of pharmacal research · 2021Review
- Expression of Components of the Renin-Angiotensin System by Cancer Stem Cells in Renal Clear Cell Carcinoma.Biomolecules · 2021Article
- Severe COVID-19 Infection Associated with Endothelial Dysfunction Induces Multiple Organ Dysfunction: A Review of Therapeutic Interventions.Biomedicines · 2021Review
- COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response.Scientific reports · 2021Article
- Clinical Implications of (Pro)renin Receptor (PRR) Expression in Renal Tumours.Diagnostics (Basel, Switzerland) · 2021Article
- Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation.International journal of biological sciences · 2021Article
- Comprehensive landscape of the renin-angiotensin system in Pan-cancer: a potential downstream mediated mechanism of SARS-CoV-2.International journal of biological sciences · 2021Article
- Screening and identification of key biomarkers of papillary renal cell carcinoma by bioinformatic analysis.PloS one · 2021Article
- Synovial fluid peptidase activity as a biomarker for knee osteoarthritis clinical progression.Bone & joint research · 2020Article
- ACE2 Protein Landscape in the Head and Neck Region: The Conundrum of SARS-CoV-2 Infection.Biology · 2020Article
- ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives.Frontiers in molecular biosciences · 2020Review
- Systematic Analysis of Coronavirus Disease 2019 (COVID-19) Receptor ACE2 in Malignant Tumors: Pan-Cancer Analysis.Frontiers in molecular biosciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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