Abstract A31: Genome-wide microRNA profiling analysis of breast cancer among African American and European American women

Abstract

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 between tumor subtypes and are associated with other clinicopathological factors, such as tumor grade and lymph node status. We identified 64 differentially expressed (mean fold change>2 and FDR<0.05) miRNAs between ER negative and ER positive tumors. Interestingly, we observed that there were 13 miRNAs differentially expressed between ER negative and ER positive breast tumors regardless of race, 28 miRNAs differentially expressed only in EA tumors and 23 miRNAs were differentially expressed in AA samples only. Specifically, the top most differentially expressed miRNAs from EA women include: several members of miR-17-92 cluster (miR-17, miR-18a, miR-19a, miR-20a), miR-508, miR509, and miR514a that are up-regulated, and miR-1, miR-133a, miR133b and miR206, which are down-regulated, in ER negative compared to ER positive tumors. In AA women, however, up-regulated miRNAs include miR-105, miR-106b, miR-135b, miR-520b; down-regulated ones include miR-216a, miR217, miR342, miR375, and miR378a. Further, several of these miRNAs, such as miR-17, miR-18a, miR-133a, miR-206, have been shown to regulate various target genes involved in apoptosis, cell cycle, invasion, or angiogenesis. 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, Lara Sucheston-Campbell, Li Tang, Jo Freudenheim, Peter Shields, Carl Morrison, Steven Belinsky, Song Liu, Kitaw Demissie, Michael Higgins, Christine Ambrosone. Genome-wide microRNA profiling analysis of breast cancer among African American and European American women. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A31.