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.
|Autori:||Schirripa, Marta; Borelli, Beatrice; D'Aurizio, Romina; Lubrano, Simone; Cremolini, Chiara; Zucchelli, Gemma; Antoniotti, Carlotta; Marmorino, Federica; Prete, Alessandra Anna; Murgioni, Sabina; Bergamo, Francesca; Zagonel, Vittorina; Tuccoli, Andrea; Marranci, Andrea; Rizzo, Milena; Tedeschi, Lorena; Magnoni, Letizia; Falcone, Alfredo; Loupakis, Fotios; Poliseno, Laura|
|Titolo:||Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib|
|Anno del prodotto:||2019|
|Digital Object Identifier (DOI):||10.1038/s41397-019-0075-3|
|Appare nelle tipologie:||1.1 Articolo in rivista|