Abstract 7467: Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis

Abstract Significant racial disparities are found in prostate cancer patients. African American (AA) individuals have a ∼64% higher incidence and 2.3 times increased mortality rate compared to Caucasian (CA) counterparts. This study integrates RNA and exome sequencing from prostate cancer tissue in both populations to uncover genetic and transcriptomic differences driving these disparities. We analyzed 52 prostate cancer samples (27 AA, 25 CA) using RNA-seq and exome sequencing. RNA-seq analysis revealed 1003 upregulated and 1589 downregulated genes in AA samples compared to CA samples. Pathway analysis showed enhanced activity in immune response and cellular interactions in AA samples, with notable regulation by histone-associated transcription factors (HIST1H1A, HIST1H1D, and HIST1H1B). X2K analysis identified enrichment of EZH2 and SUZ12 transcription factors, core components of the PRC2 complex, suggesting epigenetic regulation involvement in AA prostate cancer. Exome sequencing identified 5419 mutations unique to AA samples and 1146 unique to CA samples. After filtering race-specific variants, we identified 266 unique mutations affecting 20 genes in AA samples and 415 unique mutations impacting 21 genes in CA samples. Key genes with high-impact mutations in AA samples included TP73 (tumor suppression), XYLB (metabolism), ALDH4A1 (oxidative stress), PTPRB (cellular signaling), and HLA-DRB5 (immune response), potentially contributing to disease progression and therapy response disparities. The distinct molecular profiles identified between AA and CA prostate cancers, particularly in immune response pathways and epigenetic regulation, suggest potential therapeutic targets. These findings highlight the importance of considering genetic and epigenetic variations in developing tailored therapeutic approaches to improve treatment efficacy and reduce mortality rates across diverse populations. Citation Format: Ahmed Fadiel, Abdalla Elbialy, Akshay Sood, Shang-Jui Wang, Peng Wang, Anil V. Parwani, Gennady Shvets, Nagireddy Putluri, Jenny Li, Xuefeng Liu. Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7467.