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

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 possi...

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Published in:The pharmacogenomics journal 2019-10, Vol.19 (5), p.455-464
Main Authors: 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
Format: Article
Language:English
Subjects:
Colorectal cancer
Colorectal carcinoma
Metastases
Metastasis
MicroRNAs
miRNA
Patients
Plasma levels
Targeted cancer therapy
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Summary: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 
ISSN:1470-269X
1473-1150
DOI:10.1038/s41397-019-0075-3