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

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). Metho...

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Detalles Bibliográficos
Autores: Molina Pinelo, Sonia, Carnero, Amancio, Rivera, Fernando, Estevez-Garcia, Purificacion, Bozada, Juan Manuel, Limón, María Luisa, Paz-Ares Rodriguez, Luis, Portilla de Juan, Fernando de la, García Carbonero, Rocío
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:dnet:idus________::a0afb9fcafba19b32046b6f0f6782cf3
Acceso en línea:https://hdl.handle.net/11441/187149
https://doi.org/10.1186/1471-2407-14-656
Access Level:acceso abierto
Palabra clave:MicroRNAs
Advanced colorectal cancer
Chemotherapy response
Prediction
Descripción
Sumario: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.