Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib

Marta Schirripa, Beatrice Borelli, Romina D'Aurizio, Simone Lubrano, Chiara Cremolini, Gemma Zucchelli, Carlotta Antoniotti, Federica Marmorino, Alessandra Anna Prete, Sabina Murgioni, Francesca Bergamo, Vittorina Zagonel, Andrea Tuccoli, Andrea Marranci, Milena Rizzo, Lorena Tedeschi, Letizia Magnoni, Alfredo Falcone, Fotios Loupakis, Laura Poliseno

Research output: Contribution to journalArticlepeer-review

Abstract

Biomarkers able to improve the cost/benefit ratio are urgently needed for metastatic colorectal cancer patients that are eligible to receive regorafenib. Here, we measured plasma levels of ten circulating microRNAs (c-miRNAs) and we investigated their early changes during treatment, as well as possible correlation with clinical outcome. Ten literature-selected c-miRNAs were quantified by qRT-PCR on plasma samples collected at baseline (d1) and after 15 days of treatment (d15). C-miRNAs showing significant changes were further analyzed to establish correlations with outcome. A decision tree-based approach was employed to define a c-miRNA signature able to predict the outcome. Results achieved in an exploratory cohort were tested in a validation group. In the exploratory cohort (n = 34), the levels of c-miR-21 (p = 0.06), c-miR-141 (p = 0.04), and c-miR-601 (p = 0.01) increased at d15 compared with d1. A c-miRNA signature involving c-miR-21, c-miR-221, and c-miR-760 predicted response to treatment (p < 0.0001) and was significantly associated to PFS (HR = 10.68; 95% CI 3.2-35.65; p < 0.0001). In the validation cohort (n = 36), the increase in c-miR-21 (p = 0.02) and c-miR-601 (p = 0.02) levels at d15 was confirmed, but the associations with outcome were not. Our data indicate that early changes of c-miRNA levels might be influenced by regorafenib treatment. However, further studies are needed to establish the predictive power of such modifications.

Original languageEnglish
Pages (from-to)455-464
Number of pages10
JournalPharmacogenomics Journal
Volume19
Issue number5
DOIs
Publication statusPublished - Oct 2019

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