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.
Cancers. 2020 Jun 02*** epublish ***
Francisca Dias, Ana Luísa Teixeira, Inês Nogueira, Mariana Morais, Joana Maia, Cristian Bodo, Marta Ferreira, Alexandra Silva, Manuela Vilhena, João Lobo, José Pedro Sequeira, Joaquina Maurício, Jorge Oliveira, Klaas Kok, Bruno Costa-Silva, Rui Medeiros
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 António Bernardino de Almeida, 4200-072 Porto, Portugal., Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal., Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal., Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal., Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal., 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 António Bernardino de Almeida, 4200-072 Porto, Portugal., 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.