Abstract 6141: Understanding the role of gp78 in breast cancer health disparities

Abstract

Abstract Background: Breast cancer is a devastating disease where death rates for women of African ancestry (AA) are 40% higher than that of European ancestry (EA), demonstrating racial disparity in mortality. gp78 protein is an independent predictor of poor outcomes in women of AA that is over-expressed in aggressive breast cancers. The purpose of this research was to understand how gp78 is associated with poor survival rates by studying tumor biology and gene expression. We hypothesize a positive correlation between the overexpression of gp78 protein in higher amounts for AA women than that of European ancestry women which may correlate with specific functional pathways. Methods: Medical data was collected from a health disparities cohort in Eastern North Carolina. The patient’s race, ethnicity/ancestry were self-reported at the initial visit; the study cohort was reported as 50% AA. Immunohistochemistry to measure protein expression, DNA mutation & gene expression used with Gene Set Enrichment Analysis(GSEA) of 147 patients to identify functional pathway differences in tumor biology between high versus low gp78 expression versus gp78 expression based on patient race. Hierarchical clustered heatmaps were used to compare overlapping genes that were differentially expressed. Results: 49 common genes were identified as the overlap between the genes in the differential gene expression list for gp78 and the two different gene set enrichment analyses compared: GSEA based on patients expressing high versus low gp78 protein by IHC versus GSEA based on white vs black patients (race). The hierarchical cluster analysis of the gene expression patterns identified two prominent clusters: association by extracellular factors in the tumor microenvironment and association by mitochondrial regulation and proliferation. Conclusions: This study suggests that gp78 differences based on race may be linked to tumor microenvironment, mitochondrial function, & proliferation linking gp78 as a biomarker that is differentially expressed based on race and more highly correlated with breast cancer aggressiveness to functional properties of mitochondrial metabolism & tumor microenvironment. We will explore this gene signature/biomarker that may predict survival based on race. This discovery provides new areas of research to explore the relationship of extracellular factors in the tumor microenvironment, mitochondria regulation, & proliferation. Clinical & nonclinical interventions addressing racial health disparity in mortality should target breast cancer-specific health determinants (both environmental and biological) among those of AA with efforts to decrease racial disparities in mortality rates. These new observations indicate gp78 may be a biomarker that can predict survival based on race using tumor biology, which can contribute to new strategies for reducing the rate at which women of AA disproportionately suffer from breast cancer mortality. Citation Format: Sediqua Sherese Bufford. Understanding the role of gp78 in breast cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6141.