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Open AccessArticle

Plasma Extracellular Vesicle-Derived TIMP-1 mRNA as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma: A Pilot Study

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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
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Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
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Research Department of the Portuguese League Against Cancer Regional Nucleus of the North (LPCC-NRN), Estrada da Circunvalação 6657, 4200-177 Porto, Portugal
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Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasília, 1400-038 Lisbon, Portugal
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Graduate Program in Areas of Basic and Applied Biology (GABBA), University of Porto, 4200-135 Porto, Portugal
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Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Department of Pathology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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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
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Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
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Department of Immunology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
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Experimental Pathology and Therapeutics 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
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Faculty of Health Sciences, Fernando Pessoa University (UFP), Praça 9 de Abril 349, 4249-004 Porto, Portugal
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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
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Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4624; https://doi.org/10.3390/ijms21134624
Received: 22 May 2020 / Revised: 16 June 2020 / Accepted: 17 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Extracellular Vesicles as a New Source of Liquid Biopsy)
The tumor microenvironment has gained a lot of attention from the scientific community since it has a proven impact in the development of tumor progression and metastasis. Extracellular vesicles (EVs) are now considered one of the key players of tumor microenvironment modulation. Clear cell renal cell carcinoma (ccRCC) is the most lethal urological neoplasia and presents a high metastatic potential, which reinforces the need for the development of more effective predictive biomarkers. Our goal was to evaluate the applicability of EV-derived matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as prognostic biomarkers for ccRCC. To do so, we studied the plasma EV content of 32 patients with localized ccRCC and 29 patients with metastatic ccRCC. We observed that patients with localized disease and tumors larger than 7 cm presented higher levels of plasma EV-derived TIMP-1 mRNA when compared with patients presenting smaller tumors (p = 0.020). Moreover, patients with metastatic disease presented higher levels of EV-derived TIMP-1 mRNA when compared with patients with localized disease (p = 0.002) and when we stratified those patients in high and low levels of TIMP-1 EV-derived mRNA, the ones presenting higher levels had a lower overall survival (p = 0.030). EV-derived TIMP-1 mRNA may be a good prognostic biomarker candidate for ccRCC. View Full-Text
Keywords: clear cell Renal Cell Carcinoma; Extracellular Vesicles; TIMP-1; mRNA clear cell Renal Cell Carcinoma; Extracellular Vesicles; TIMP-1; mRNA
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Dias, F.; Teixeira, A.L.; Nogueira, I.; Morais, M.; Maia, J.; Bodo, C.; Ferreira, M.; Vieira, I.; Silva, J.; Lobo, J.; Sequeira, J.P.; Maurício, J.; Oliveira, J.; Palmeira, C.; Martins, G.; Kok, K.; Costa-Silva, B.; Medeiros, R. Plasma Extracellular Vesicle-Derived TIMP-1 mRNA as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma: A Pilot Study. Int. J. Mol. Sci. 2020, 21, 4624.

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