Join the Gibco Cell Culture Heroes webinar featuring Heather Beasley, PhD as she presents "SLC25A46 as a Novel Mitochondrial Regulator and Biomarker in Breast Cancer."

 

Triple-negative breast cancer (TNBC) is an aggressive, highly malignant breast cancer (BC) subtype further characterized by poor prognosis and chemoresistance. TNBC disproportionately affects African American and Latina women, wherein this study we account for the role of ancestry in BC prognosis and progression. We hypothesize that ancestry has significant influences on BC etiology. Metabolic reprogramming of TNBC cells is shown to influence response to treatments, which requires the proper function of the mitochondrion. To this end, we sought to investigate SLC25A46, a poorly characterized mitochondrial protein. We were interested if SLC25A46 has any potential as a target or biomarker in BC. First, we applied PrediXcan, a gene-based statistical algorithm, to calculate genetically predicted gene expression for SLC25A46 in 70,349 patients of European descent and 14,462 patients of African descent in BioVU, the Vanderbilt University Medical Center (VUMC) biorepository linked to de-identified electronic health records (EHRs). We observed that patients with high predicted expression were more likely to receive diagnosis of ‘abnormal findings in mammograms’ (P=2.76E-06, OR=2.26) or ‘lump or mass in breast’ (P=8.9E-06, OR=2.61) in the European descent group. Therefore, we investigated SLC25A46 expression in an international RNAseq cohort enriched with women of African ancestry. Interestingly, SLC25A46 shows significantly higher expression among self-reported AA than Ghanaian or Ethiopian women with TNBC (P=0.003). Thus, we postulated that these differences in SLC25A46 for patients of African ancestry might serve as a novel biomarker for cancer outcomes. Together, these data suggest that SLC25A46 has implications in BC as a novel target in cancer development, specifically in patients with admixed ancestry.

 

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