%0 Journal Article
%T Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib
%J -
%D 2019
%R https://doi.org/10.1038/s41397-019-0075-3
%X 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¨C35.65; 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
%U https://www.nature.com/articles/s41397-019-0075-3