Evaluation of microRNA-10b expression as a novel predictive marker of metastases development and patients’ survival in breast cancer.

MicroRNA-10b was found highly expressed in metastatic breast cancer cell lines and able to generate metastases in mice models. The aim of this study is to evaluate the putative association between miR10b expression and disease progression. Methods: We selectedfrom our tumor bank 150 consecutive breast cancers with at least three years follow up. For each case frozen paired tumor and normal tissue and complete clinical data were available. Pathological examination was performed to ensure that each tumour sample contained more than 70% of cancer cells resulting in 114 samples suitable for RNA extraction. RNA quality was measured and only samples with RIN≥7.0 were analyzed (n=101) by a relative quantification method. Results: miR10b relative expression in tumor to normal samples (RERs) was significantly higher in the subgroup of patients with metastases (median 0.25 IQR 0.11-1.02) as compared with patients without metastases (median 0.09 IQR 0.04-0.29) (P=0.023 Mann Whitney Test). The association between miR-10b RERs and survival was evaluated in the group of patients without metastases at diagnosis (n=90). In univariate Cox regression model, patients with high miR-10b RERs had a higher risk of distant metastases development (HR 4.91, P=0.02) and disease related death (HR 6.02; P=0.01). In a multivariate Cox regression model adjusted for tumor size, lymph node metastases, grade, ER, PgR status, and Ki67 labeling index (n=79), higher miR-10b RERs were still associated with increased risk of distant metastases development (HR18.84; P<0.001) and disease related death (HR 13.39; P=0.003) (Table). Conclusions: We show that in breast cancer patients miR-10b expression is associated with worse prognosis on a short term follow up. These results suggest that miR-10b expression could be used for individual patient’s risk assessment and perhaps as potential therapeutical target.