Abstract 1960: Identification of differentially expressed miRNAs of breast cancer among African American and European American women

Abstract

African American (AA) women are more likely than European American (EA) women to be diagnosed with aggressive, estrogen receptor (ER) negative breast cancer. Differences in microRNA (miRNA) expression patterns have not been well studied as potential mechanisms underlying this racial disparity. In this study, we performed a whole-genome miRNA expression profiling in 58 (29 AA and 29 EA) fresh-frozen breast tumors, with clinical characteristics (e.g., ER status, histological grade, stage) comparable between AA and EA samples, and in 10 (5 AA and 5 EA) normal breast tissues obtained from women undergoing reduction mammoplasty, with pathology determined free from any abnormalities. Unsupervised hierarchical clustering showed that miRNA expression patterns clearly distinguish breast cancer from normal breast tissue. In tumors, a number of miRNAs are significantly differentially expressed, i.e., DEmiRs defined as >2-fold change in expression and FDR<0.05, between tumor subtypes and by race. We identified 61 DEmiRs between ER negative and ER positive breast tumors; of these, 14 miRNAs were differentially expressed regardless of race; 29 miRNAs were specific in EA tumors only; and 18 were in AA samples only. Specifically, the top most differentially expressed miRNAs from EA women include: several members of miR-17-92 cluster (miR-17,-18a,-19a, -20a), miR-508, -509,and -514a that are up-regulated, and miR-1, -133a, -133b, and -206, which are down-regulated, in ER negative compared to ER positive tumors. In AA women, however, up-regulated miRNAs include miR-105, -106b, -135b, and -520b; down-regulated ones include miR-216a, -217, -1303, and -378a. We also identified 14 DEmiRs between AA and EA tumor samples, with 5 miRNAs specific in ER- tumors, such as miR-9, -106b, and 9 miRNAs in ER+ tumors, such as miR-1, -133a, -133b, and -206. Further, several of these miRNAs, such as miR-17, miR-18a, miR-133a, miR-206, miR-9, have been shown to regulate various target genes involved in apoptosis, cell cycle, invasion, or angiogenesis. We also found that several miRNAs, such as miR-1, -133a, -216a, are associated with improved or reduced recurrence-free or overall survival. In summary, in this genome-wide miRNA expression profiling analysis by next generation sequencing, our results suggest that miRNA expression patterns may differ by tumor subtypes between AA and EA breast samples. These initial results will provide the basis for the functional analysis of the identified miRNAs, and findings could contribute to a better understanding of the biology of breast cancer disparities and more targeted preventative and therapeutic strategies. Citation Format: Zhihong Gong, Dan Wang, Allyson Espinal, Qiang Hu, Xuan Peng, Lara Sucheston-Campbell, Li Tang, Jo Freudenheim, Peter Shields, Carl Morrison, Steven Belinsky, Song Liu, Kitaw Demissie, Michael Higgins, Christine Ambrosone. Identification of differentially expressed miRNAs of breast cancer among African American and European American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1960.