Differential Gene Expression Profiles of Pancreatic Ductal Adenocarcinomas Among African American and Caucasian American Patients

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths. In the United States (US), African Americans (AA) have higher PDAC incidence and mortality than Caucasian Americans (CA). This study aimed to identify distinct gene expression patterns and differentially regulated pathways in AA and CA PDACs. METHODS: Whole transcriptomic analyses were conducted on FFPE sections of PDACs (n=40) from AA (9 PDAC/3 normal) and CA (31 PDAC/5 normal) tissues to evaluate differential expression and signaling pathways within and between racial groups and to identify distinctive and common genes/pathways. RESULTS: We identified uniquely upregulated genes in both racial groups. Among the 25 top upregulated genes in AA PDACs, compared to their normal tissues, were CHST15, PARP15, and NUDT16. Altered pathways in AA PDACs included glycerophospholipid metabolism and regulation of lipolysis in adipocytes. In contrast, a different set of top 25 upregulated genes was found in CA PDACs, including SERPINB3, PADI1, H3C8, and ZNF488. The altered pathways in CA PDACs included cellular senescence and PD−L1/PD−1 checkpoint pathways. Thirteen genes (seven upregulated and six downregulated) were differentially modulated in AA vs. CA PDACs. Using a publicly available database, we analyzed the top 25 upregulated genes (normal vs. tumor) and seven differentially upregulated genes (AA vs. CA) for associations with survival outcomes. Eight genes (CHST15, PARP15, NUDT16, SERPINB3, PADI1, H3C8, ZNF488, and LETM2) correlated with poor survival. CONCLUSION: These findings show distinct gene expression profiles and modulated pathways in AA and CA PDACs, supporting development of race-based therapeutic targets.