MicroRNAs as potential predictors of extreme response to tyrosine kinase inhibitors in renal cell cancer

• Published in: Urologic oncology 2020-07, Vol.38 (7), p.640.e23-640.e29
• Main Authors: Garrigós, Carmen, Molina-Pinelo, Sonia, Meléndez, Ricardo, Espinosa, Marta, Lerma, Antonio, Taron, Miguel, García-Donas, Jesús, Rodriguez-Antona, Cristina, Duran, Ignacio
• Format: Article
• Language: English
• Subjects: Biomarker; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Female; Gene expression; Humans; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Male; MicroRNAs - genetics; Middle Aged; miRNAs; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Renal Cell Carcinoma; Tyrosine kinase inhibitors
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2020.01.012

•Patients with metastatic renal cancer cell (mRCC) and extreme response to tyrosine kinase inhibitors (TKIs) showed different miRNAs expression in this analysis.•Mir-139-3p, miR-let7e, miR-let7d were down-regulated in patients that showed primary resistance to treatment vs. long-responders patients.•Inversely miR-425-5p was up-regulated in patients presenting primary resistance to treatment vs. long-responders.•There might be a role for these miRNAs to predict outcomes in mRCC patients treated with TKIs. MicroRNAs play an important role as modulators of gene expression in several biological processes and are closely related to development and cell differentiation regulation. Previous works have revealed a potential predictive role for miRNAs in different tumor types. This study aims to analyze the ability of miRNAs in segregating metastatic renal cell carcinoma patients according to their responses to tyrosine kinase inhibitors (TKIs). Extreme responders were considered in the study and were defined as those patients that either had a long-term response (LR) (progression-free survival ˃11 months) or those that were primary refractory (PR) (progression as best response). The expression of 754 miRNAs was analyzed in tumor tissue of these 2 sets of patients. In a study cohort (n = 15) 4 miRNAs were significantly associated with patient response and differentially expressed in PR vs. LR (up-regulated in PR vs. LR: miR-425-5p, down-regulated in PR vs. LR: miR-139-3p, let-7d and let-7e). Further analysis in a validation cohort (n = 36) revealed similar results. The present data strength the potential role of miRNAs as a tool to predict treatment outcomes in patients with metastatic renal cell carcinoma treated with TKIs.