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

The Pharmacogenomics Journal volume 19, pages 455–464 (2019)Cite this article

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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.

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Acknowledgements

This work was supported by: Istituto Toscano Tumori; IIT Laboratory of Integrative Systems Medicine (LISM); FONDAZIONE ARCO; Regione Veneto [RP-2014-00000395, Caratterizzazione molecolare dei tumori del colon retto metastatico e valutazione di outcome: progetto di rete], and PRIN 2010 [Ottimizzazione dei trattamenti personalizzati con le terapie con farmaci a bersaglio molecolare nel cancro del colon retto].

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Author notes

  1. These authors contributed equally: Marta Schirripa, Beatrice Borelli, Romina D’Aurizio

  2. These authors contributed equally: Fotios Loupakis, Laura Poliseno

Authors and Affiliations

  1. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy

    Marta Schirripa, Alessandra Anna Prete, Sabina Murgioni, Francesca Bergamo, Vittorina Zagonel & Fotios Loupakis

  2. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Italy

    Beatrice Borelli, Chiara Cremolini, Gemma Zucchelli, Carlotta Antoniotti, Federica Marmorino & Alfredo Falcone

  3. Institute of Informatics and Telematics, CNR, Pisa, Italy

    Romina D’Aurizio

  4. Institute of Clinical Physiology, CNR, Pisa, Italy

    Simone Lubrano, Andrea Tuccoli, Andrea Marranci, Milena Rizzo, Lorena Tedeschi & Laura Poliseno

  5. Oncogenomics Unit, CRL-ISPRO, Pisa, Italy

    Simone Lubrano, Andrea Tuccoli, Andrea Marranci & Laura Poliseno

  6. Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I University Hospital, Rome, 00100, Italy

    Alessandra Anna Prete

  7. Biostatistics consultant, Siena, Italy

    Letizia Magnoni

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  1. Marta Schirripa
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Correspondence to Laura Poliseno.

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Schirripa, M., Borelli, B., D’Aurizio, R. et al. Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib. Pharmacogenomics J 19, 455–464 (2019). https://doi.org/10.1038/s41397-019-0075-3

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