miR-187 is an independent prognostic factor in breast cancer and confers increased invasive potential in vitro
Menée sur des lignées cellulaires et deux cohortes de 117 et 470 patientes atteintes d'un cancer du sein, cette étude évalue l'association entre l'expression du micro-ARN 187 et le pronostic de la maladie
Purpose Here, we describe an integrated bioinformatics, functional analysis and translational pathology approach to identify novel miRNAs involved in breast cancer progression. Experimental Design Co-inertia analysis was used to combine a database of predicted miRNA target sites and gene expression data. Using two independent breast cancer cohorts, CIA was combined with correspondence analysis and between group analysis to produce a ranked list of miRNAs associated with disease progression. Ectopic expression studies were carried out in MCF7 cells and miRNA expression evaluated in two cohorts of breast cancer patients by in situ hybridisation on tissue microarrays. Results CIA identified miR-187 as a key miRNA associated with poor outcome in breast cancer. Ectopic expression of miR-187 in breast cancer cells resulted in a more aggressive phenotype. In a test cohort (n=117), high expression of miR-187 was associated with a trend towards reduced breast cancer-specific survival (BCSS) (p=0.058), and a significant association with reduced BCSS in lymph node-positive patients (p=0.036). In a validation cohort (n=470), high miR-187 was significantly associated with reduced BCSS in the entire cohort (p=0.021) and in lymph node-positive patients (p=0.012). Multivariate cox regression analysis revealed that miR-187 is an independent prognostic factor in both cohorts [Cohort 1 HR-7.37 (95%CI 2.05-26.51, p=0.002); Cohort 2 HR-2.80 (95%CI 1.52-5.16, p=0.001)] and in lymph node-positive patients in both cohorts [Cohort 1 HR-13.74 (95%CI 2.62-72.03, p=0.002); Cohort 2 HR-2.77 (95%CI 1.32-5.81, p=0.007)]. Conclusions miR-187 expression in breast cancer leads to a more aggressive, invasive phenotype and acts as an independent predictor of outcome.
Clinical Cancer Research , résumé, 2012