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miRNA Expression in African Americans with Quadruple Negative Breast Cancer Shapes Overall Survival

Our lab recently identified that a subset of TNBC patients also lack Androgen Receptor (AR) and we named this breast cancer subtype “Quadruple Negative breast cancer” (QNBC). QNBC tumors are commonly found in younger AA women and have worse outcomes compared to other breast cancer subtypes. Additionally, QNBC tumor are predominately associated with basal-like and immunomodulatory (IM) subtypes in African American women. In this study we sought to identify the underlying mechanisms associated with the QNBC subtype. To understand this subtype further, we sought to determine the miRNA–mRNA profile in QNBC patients based on race. Utilizing two large independent gene expression breast cancer datasets, we found miRNA-mRNAs interactions which include FOXA1 and MYC (mir-17/20a targets); GATA3 and CCNG2 (mir-135b targets); CDKN2A, CDK6, and B7-H3 (mir-29c targets); and RUNX3, KLF5, IL1-β, and CTNNB1 (mir-375 targets) were correlated with basal-like and immune subtypes in QNBC patients and associated with a worse survival. Furthermore, each of these mRNA was validated protein levels using proteomics dataset. Thus, our findings suggest that QNBC tumors have race specific altered gene signature that is implicated in racial disparity and poor survival in African American women with breast cancer.

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