{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:57:36Z","timestamp":1773338256631,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE-01-0247-FEDER-033399"],"award-info":[{"award-number":["NORTE-01-0247-FEDER-033399"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011776","name":"Instituto Portugu\u00eas de Oncologia do Porto","doi-asserted-by":"publisher","award":["CI-IPOP-21-2015"],"award-info":[{"award-number":["CI-IPOP-21-2015"]}],"id":[{"id":"10.13039\/501100011776","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC.<\/jats:p>","DOI":"10.3390\/cancers12061450","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T04:12:09Z","timestamp":1591157529000},"page":"1450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-4467","authenticated-orcid":false,"given":"Francisca","family":"Dias","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB2, E Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"}]},{"given":"Ana Lu\u00edsa","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB2, E Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"In\u00eas","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB2, E Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"},{"name":"Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"}]},{"given":"Mariana","family":"Morais","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB2, E Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"},{"name":"Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"}]},{"given":"Joana","family":"Maia","sequence":"additional","affiliation":[{"name":"Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Bras\u00edlia, 1400-038 Lisbon, Portugal"},{"name":"Graduate Program in Areas of Basic and Applied Biology (GABBA), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Cristian","family":"Bodo","sequence":"additional","affiliation":[{"name":"Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Bras\u00edlia, 1400-038 Lisbon, Portugal"}]},{"given":"Marta","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Alexandra","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Manuela","family":"Vilhena","sequence":"additional","affiliation":[{"name":"Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB3, F Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-3347","authenticated-orcid":false,"given":"Jos\u00e9 Pedro","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB3, F Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Joaquina","family":"Maur\u00edcio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7838-7493","authenticated-orcid":false,"given":"Jorge","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-3439","authenticated-orcid":false,"given":"Klaas","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen (UMCG), University of Groningen, Hanzeplein 1, 9713 GZ Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-6211","authenticated-orcid":false,"given":"Bruno","family":"Costa-Silva","sequence":"additional","affiliation":[{"name":"Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Bras\u00edlia, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Research Center- LAB2, E Bdg 1st floor, Rua Dr Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal"},{"name":"Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvala\u00e7\u00e3o 6657, 4200-177 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Biomedical Research Center (CEBIMED), Faculty of Health Sciences of Fernando Pessoa University (UFP), Pra\u00e7a 9 de Abril 349, 4249-004 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.celrep.2018.03.075","article-title":"The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma","volume":"23","author":"Ricketts","year":"2018","journal-title":"Cell Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S0140-6736(15)00046-X","article-title":"Renal cancer","volume":"387","author":"Capitanio","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.eururo.2016.02.029","article-title":"The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours","volume":"70","author":"Moch","year":"2016","journal-title":"Eur. 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