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

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., Jul-2020, In : International Journal of Molecular Sciences. 21, 13, p. 1-17 17 p., 4624.

Research output: Contribution to journalArticleAcademicpeer-review

  • Francisca Dias
  • Ana Luísa Teixeira
  • Inês Nogueira
  • Mariana Morais
  • Joana Maia
  • Cristian Bodo
  • Marta Ferreira
  • Isabel Vieira
  • José Silva
  • João Lobo
  • José Pedro Sequeira
  • Joaquina Maurício
  • Jorge Oliveira
  • Carlos Palmeira
  • Gabriela Martins
  • Klaas Kok
  • Bruno Costa-Silva
  • Rui Medeiros

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.

Original languageEnglish
Article number4624
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume21
Issue number13
Publication statusPublished - Jul-2020

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