Abstract PO-005: Proteome profiling of pancreatic ductal adenocarcinoma (PDAC) primary tumors in Caucasian, African American and Latinx patients

The clinical management of pancreatic ductal adenocarcinoma (PDAC) faces difficult challenges due to its aggressive metastatic potential, complex microenvironment, and lack of targeted therapies. Health disparities also exacerbate these challenges. For instance, African and African Americans have higher incidence rates and worse clinical outcomes than Whites even when socioeconomic and tumor stages are controlled. To advance the understanding of the biological differences across the racial groups, the PDAC primary tumors collected from 30 Caucasian, 12 African American (AA) and 3 Latinx patients were analyzed by quantitative proteomics. In collaboration with the IDeA National Resource for Quantitative Proteomics, 5820 proteins were identified and quantified using data-independent acquisition (DIA) in the tumor proteome. Comparing the Latinx and the Caucasian tumor proteome, 120 and 95 proteins were found up- and down-regulated in the Latinx proteome. Proteins involved in the fatty acid metabolism, urea cycle, bile acid and bile salt metabolism were found enriched among the upregulated proteins. 108 and 75 proteins were found up- and down-regulated in African American tumor proteome over the Caucasians. The 108 upregulated proteins were submitted for Reactome Pathway Analysis. Pathways such as the complement cascade, extracellular matrix organization and ECM proteoglycans were found enriched. Haptoglobin-related protein (HPR) was one of the 108 upregulated proteins in the AA tumor proteome, which is also observed at the transcript level in the TCGA data. The HPR is known for its trypanolytic function and gene amplifications are observed in those of African descent. HPR works with haptoglobin (HP) to clear the free hemoglobin in blood to prevent oxidative damage. We believe that the proteins overexpressed, and the biological processes activated are contributing to the PDAC disparities observed in the African descendants. Therefore, the characterization of the PDAC proteome is a valuable method to delineate the underlying molecular signatures that may contribute to the health disparities. Citation Format: Henry C. H. Law, Andrea N. Riner, Jose G. Trevino, Nicholas T. Woods. Proteome profiling of pancreatic ductal adenocarcinoma (PDAC) primary tumors in Caucasian, African American and Latinx patients [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-005.