Abstract 168: Differential microRNA expression profiles of breast cancer and matched benign breast samples stratified by ER status
Authors: Costa Fabricio F. , Bischof Jared M. , Scholtens Denise , Sullivan Megan E. , Ivancic David Z. , Vanin Elio F. , Soares Marcelo B. , Khan Seema A. 
Published: June 2012

Abstract
Background: The identification of women at high risk for breast cancer remains a challenge. Robust risk markers that better stratify women for their probability of developing breast cancer would represent a significant advance for breast cancer prevention research. microRNAs (miRNAs) are a large group of non-coding RNAs, generally 18-25 nt long, which block messenger RNA (mRNA) translation and affect mRNA stability. Since the molecular signature of ER-positive breast cancer differs from that of ER-negative breast cancer, we hypothesized that miRNA profile differences may be reflected in the contralateral normal breast tissue of women with breast cancer.Methods:we used a well-annotated set of samples comprised of matched contra-lateral benign breast tissue (MCBB) from 30 women (15 ER positive and 15 ER negative tumor with their corresponding MCBBs matched for age and race) to generate expression profiles of 754 mature miRNAs by TaqMan Low Density Arrays (TLDAs). Following background subtraction, miRNA levels were normalized against controls and compared across groups using tests of contrast on estimated parameters from a full ANOVA model with Empirical Bayes variance correction and False Discovery Rate (FDR) control at p≪0.05 using the Benjamini-Hochberg method. Following this strategy, we have performed different pair-wise comparisons as follows: 1) ER+ to ER- tumors, 2) ER+ tumor to MCBB tissue, 3) ER- tumor to MCBB, and 4) MCBB tissue from women with ER+ versus ER- tumors.Results: We observe clear patterns of differential expression between ER+ and ER- tumors. Four miRNAs were significantly down-regulated in ER+ tumors compared to ER-negative, whereas miR190b was significantly up-regulated in ER- lesions. More striking were the patterns of differential expression of 23 miRNAs in ER- breast cancer tissue compared to MCCB. A similar analysis in ER+ breast cancer and MCBB yeilded at least 29 miRNAs with significantly differential expression. Among these differentially expressed miRNAs, nine miRNAs were common in the ER- and ER+ cancers, and the remainder were distinct. Notably, we found that miR-18a and miR-18b expression were more than 50-fold higher in ER- cancer samples compared to MCBB, but when we compared ER+ tumor to MCBB, we found no significant difference in miR-18b expression. On the other hand, miR-96 and miR-183 are over-expressed in both ER+ and ER- tumors when compared to the MCBB set. Comparing MCBB from women with ER-and ER+ breast cancer yielded no significant differences. Conclusion: we see striking differences in the patterns of miRNA expression differences between breast cancer samples and matched contralateral benign tissue when stratified by ER status.The majority of the miRNAs identified in our analyses are novel. These findings have significant potential for the identification of new ER- status specific and biologically significant molecular biomarkers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 168. doi:10.1158/1538-7445.AM2011-168