In the U.S., the incidence rates of breast cancer (BC) among Caucasian (CA) women are lower than those of African American (AA); however, AA women have a significantly higher mortality rate. It is imperative that we continue to investigate the underlying molecular biology that may contribute to the cause of health disparities between AA and CA with TNBC. In this study, gene expression profiling, using the Almac BC DSA Research Tool, was performed on archived FFPE samples, obtained from CA and AA women diagnosed with early-stage (Node 0) TNBC. Unsupervised hierarchical clustering revealed a pattern of differential gene expression in the AA cohort compared to CA. Using a subtyping Tool for TNBC, we found a distinct distribution pattern of TNBC molecular subtypes in the AA cohort, which was very different than the CA cohort: basal-like (14%), immunomodulatory (43%) and mesenchymal (43%). Gene expression analyses, comparing the AA and CA cohort (fold change > 2.0, p-value <.05), resulted in 190 differentially expressed genes (DEG). Pathway enrichment analysis conducted in MetaCore GeneGo revealed that the DEGs were over-represented in cytoskeletal remodeling, cell adhesion, tight junctions, and immune response in the AA TNBC cohort. Furthermore, several genes in the Wnt/β-catenin pathways were overexpressed in the top 10 enrichment pathways. We validated our results using RT-qPCR and identified Caveolin-1 (CAV1) as being significantly expressed in the AA-TNBC cohort (p-value 1.22 x 10-05). An independent cohort of FFPE samples, from AA and CA women with early stage TNBC, was used to create a tissue microarray (TMA). Immunohistochemistry results showed no difference in subcelluar localization of Cav1 between the AA and CA cohorts; however, the AA cohort had significantly higher levels of Cav1 staining (p-value 0.04). Additionally, using RT-qPCR, we demonstrated that CAV1 mRNA was significantly higher in the AA TNBC cohort (p-value 0.48). Furthermore, endogenous Cav1 was shown to be highly expressed in a cell line panel of TNBC, in particular, those of the mesenchymal and basal-like molecular subtypes. Finally, using siRNA, we demonstrated that CAV1 silencing resulted in a significant decrease in cell proliferation for each of the TNBC cell lines while it showed no effect on the luminal ER+ cell lines. Our combined study results suggest that CAV1 overexpression may be a biologic contributor to the observed health disparity between AA women and CA diagnosed with early-stage TNBC.
Citation Format: Lisa L. Baumbach-Reardon, Julie Getz, Mary E. Ahearn, John Carpten, Mark Pegram. High caveolin-1 expression in African American women with early-stage triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4352.