Abstract 5810: microRNAs targeting EMT transcription factors may be associated to lymph node metastasis in breast cancer tumors

Abstract

Abstract Breast cancer is the leading cause of cancer-associated deaths in women. Lymph node near to the primary breast tumor have a high chance of developing a secondary tumor, representing one of the first signs of metastasis in breast cancer. Metastasis is promoted by epithelial-mesenchymal transition (EMT), process leaded by the transcription factors SNAIL, SLUG, ZEB and TWIST. MicroRNAs are small non-coding RNAs, whose expression has been demonstrated to be altered in different cancer types. Because of their ability to regulate large sets of genes involved in cancer growth and metastasis, microRNAs have emerged as candidate molecular biomarkers and novel therapeutic targets. The aim of this study is to identify microRNAs differentially expressed in breast tumors in relation to EMT-transcription factor expression and lymph node metastasis, and that are involved in epithelial-mesenchymal transition. For this purpose, we used microRNA microarray data from 50 fresh frozen breast tumors with different tumor grades (1 to 3), 28 from patients with lymph node metastasis. Microarray data analysis using RankProd (R package) revealed approximately 40 microRNAS down-regulated in breast tumors with expression of EMT-transcription factors (p<0.05). Several of the identified microRNAs have been previously described to regulate early steps of metastasis in different cancer types, like members of the miR-200 family (miR-200c and miR-141), miR-205 and miR-30a. In addition we found other microRNAs not previously associated to metastasis. Our results suggest that down regulation of specific microRNAs, and up regulation of their targets, may induce a metastatic behavior of tumor cells of the primary breast tumors, promoting invasion and colonization of the lymph nodes. In this sense, the changes in the expression of microRNAs may serve as biomarkers of breast cancer prognosis in patients. Citation Format: Elisa Pérez-Moreno, Gabriela Valarezo, Valentina Zavala, Wanda Fernández, Pilar Carvallo. microRNAs targeting EMT transcription factors may be associated to lymph node metastasis in breast cancer tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5810. doi:10.1158/1538-7445.AM2017-5810