Discovery and validation of small RNAs predictive of aggressiveness in breast cancer

Abstract

Breast cancer is the women's second cause of deaths in the world. The few molecular markers used in the clinical breast cancer diagnosis are still not enough to allow the most adequate clinical and surgical treatment. The genetic heterogeneity presented in the patients and in the tumors also limit the prediction of clinical outcome during the evolution of the disease. In this sense, the search tumor aggressiveness markers are still very relevant. In the present project, we propose the investigation of the putative roles of small RNAs, including microRNAs (miRNAs), small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs), as putative breast cancer markers of aggressiveness. Small RNAs isolated from 50 women's tumors with invasive ductal carcinoma (Her2+, PR-, ER-) will be evaluated by large-scale sequencing using the SOLiD 4.0 plataform. Tumor samples from two groups of women regarding aggressiveness and paired by age, lymph node status and citokeratins expression will be evaluated. Small RNA libraries will be tagged to allow later samples identification. The sequences obtained will be mapped and quantitatively and qualitatively evaluated, allowing the small RNA expression analysis of the tumor samples. The small RNAs with high and consistent differential expression will be confirmed by Real-Time PCR (qPCR) and validated in a breast cancer cell-line panel with distinct migration, invasion and metastasis properties. In this way, our goal is to contribute with the identification of new small RNAs and new putative aggressiveness breast cancer markers. (AU)