Abstract P1-05-05: The effect of microRNA dysregulation on health disparities observed in African American women in triple negative breast cancer

Abstract

Abstract BACKGROUND: Triple-negative breast cancers (TNBC) represent an important subtype characterized by an absence of ER, PR, and HER2, and therefore are not responsive to current targeted therapies. TNBC is considered a clinically aggressive subtype of breast cancer with lower survival rates and a higher risk of metastasis development. There is a higher prevalence of TNBC in women of African descent. Furthermore, there is evidence that African American (AA) women have worse clinical outcomes compared with Caucasian American (CA) women with TNBC. Several studies have begun to evaluate the major drivers of this health disparity including socio-economic status, cultural influences, and biological factors; however, to date, researchers have not been able to elucidate the mechanisms behind the aggressive biology seen in AA women with TNBC. Recently miRNAs were identified to play a role in breast cancer through the regulation of cellular processes associated with aggressive tumor phenotypes, such as TNBC. MiRNAs are a likely therapeutic target because they are involved in the regulation of several essential functions in cancer cells such as proliferation, migration, invasion, and apoptosis. For miRNAs to reliably be used as cancer therapeutic agents in clinical settings, miRNA signatures of specific cancer subtypes based on ethnicity must be identified. Here, we hypothesize that differential expression of miRNAs contributes to the more aggressive phenotype observed in AA patients compared to CA patients with TNBC. In this study, our primary goal is to characterize and compare the miRNA expression profiles of breast tumor tissue from AA and CA patients. METHODS: miRNA expression data of TNBC patients, contained in the TCGA database, were analyzed to identify a set of miRNAs with prognostics significance to be used as potential biomarkers. From the acquired miRNA-seq data we determined a total of 175 differentially expressed miRNAs between AAW and CA triple negative breast cancer tissue and decided to characterize 8 miRNAs that have been previously determined to have a role in breast cancer. RESULTS: In AA tumor tissue there was the marked loss of the following tumor suppressors: let-7b, miR-200b,-130b, and -375 and the overexpression of the following oncogenic miRNAs: miR-181c, 17, 21, 29c. In TNBC, miR-200 and 130b are known to sensitize cells to apoptosis, inhibit metastasis formation, and are associated with patient survival. Additionally, the expression of oncogenic miRNAs; miR-181c, 17, 21, 29c are associated with worse prognosis in TNBC. Target gene prediction using miRBase revealed that several of the dysregulated miRNAs were involved in the epithelial-mesenchymal transition, a key step in metastasis formation. Next, we evaluated how miRNA dysregulation could potentially affect patient survival. Using data from the TCGA we were able to extrapolate survival probability data (combined CAW and AAW n=203). We determined that 5-year survival was significantly decreased in patients that had high expression of miR-181c and miR-17 and let-7b and miR-200b had protective effects. CONCLUSIONS: These results support that there is a distinct miRNA expression signature in AAW and CAW with TNBC which may correlate to prognosis. Our results will contribute to the application of miRNAs as novel therapeutic tools against TNBC in AA patients and represents an innovative approach to address the health disparities seen in the AA population. Citation Format: Ches'que M. Phillips, Yaguang Xi. The effect of microRNA dysregulation on health disparities observed in African American women in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-05.