MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer

Abstract

Molina-Pinelo, Sonia et al.[Background] MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC).[Methods] We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was analysed by RT-qPCR in an independent cohort. For a set of selected miRNAs, bioinformatic target predictions and pathway analysis were also performed.[Results] Eight miRNAs (let-7 g*, miR-107, miR-299-5p, miR-337-5p, miR-370, miR-505*, miR-889 and miR-99a-3p) were significant predictors of response to chemotherapy in the training cohort. In addition, overexpression of miR-107, miR-337-5p and miR-99a-3p, and underexpression of miR-889, were also significantly associated with improved progression-free and/or overall survival. MicroRNA-107 and miR-99a-3p were further validated in an independent cohort as predictive markers for chemotherapy response. In addition, an inverse correlation was confirmed in our study population between miR-107 levels and mRNA expression of several potential target genes (CCND1, DICER1, DROSHA and NFKB1).[Conclusions] MiR-107 and miR-99a-3p were validated as predictors of response to standard fluoropyrimidine-based chemotherapy in patients with mCRC. © 2014 Molina-Pinelo et al.; licensee BioMed Central Ltd.RGC is funded by Fondo de Investigación Sanitaria (PI10/02164), Servicio Andaluz de Salud (PI-0259/2007) and RTICC (R12/0036/0028). SM-P is funded by Fondo de Investigación Sanitaria (CD1100153) and Fundación Científica de la Asociación Española Contra el Cáncer. MDP is funded by Fondo de Investigación Sanitaria (CD0900148). AC lab was supported by grants to from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028), Consejeria de Ciencia e Innovacion (CTS-6844) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012).Peer Reviewe