Abstract 3617: Distinct immune signature and regulated genes in prostate cancer disparity
Authors: Shiv Shankar Verma, Pingfu Fu, Gregory T MacLennan, Lee E Ponsky, Chen-Han Wilfred Wu, Jonathan E Shoag, Sanjay Gupta
Journal: Cancer Research (2025)

Abstract Prostate cancer is a biologically and clinically diverse disease, with incidence and mortality rates varying significantly among different racial and ethnic groups. In African American (AA) men, the incidence of prostate cancer is approximately 60% higher, and the mortality rate is two to three times greater compared to Caucasian American (CA) men. These disparities are complex and encompass various biological and social determinants, including genetic predisposition, comorbid conditions, socioeconomic status, and environmental influences. The interplay of these elements has a clear association with disease outcomes. Recent research highlights the role of the tumor immune landscape and its associated genes in regulating prostate cancer biology at every stage of progression, ultimately impacting patient outcomes. We hypothesize that variations in immune cell gene signatures within tumors across different racial groups may influence prostate cancer outcomes. To investigate this, we analyzed transcriptomic data from 35 radical prostatectomy specimens obtained from treatment-naive patients, comprising 20 AA men and 15 CA men with prostate cancer. This analysis focused on the gene expression profiles of primary prostate tumors and adjacent normal tissues. We specifically selected immune-related genes to assess the immune-oncological differences between AA and CA prostate tumors, utilizing bioinformatics platforms such as EPIC, xCell, and IPA. To evaluate race-specific differential gene expression, we employed a rank test, and the effect of each gene’s expression on overall survival was further analyzed using a univariate Cox regression model. Prostate tumors in AA patients exhibit significant enrichment in the tumor microenvironment and a distinct gene immune profile compared to those in CA men. In AA patients we observed elevated z-scores in pathways such as CREB signaling, Th1 and Th2 pathways, dendritic cell maturation, IL-17 signaling, TREM1 signaling, and cytokine production in macrophage and T Helper cells mediated by IL-17A and IL-17F. We also noted increased cytokine levels in epithelial cells influenced by IL-17A and IL-17F. Conversely, pathways like PD-1, PD-L1, ILK, IL-3, chemokine signaling, adrenomedullin, erythropoietin signaling, IGF-1, VEGF, and B-cell receptor signaling exhibited low z-scores in AA prostate tumors. Additionally, our analysis identified 13 major immune cell types, and 27 genes significantly associated with immune cell infiltration in AA prostate cancer. The expression levels of ARSL, BAALC, CCL23, EPHA2, IGFL2, KRT5, NTM, and NDP (p &amp;lt; 0.05) were linked to overall survival in AA prostate cancer patients. Taken together, prostate cancer in AA patients demonstrates a unique immune repertoire and gene profile, characterized by significant enrichment in pro-inflammatory immune pathways that correlate with poorer outcomes. Citation Format: Shiv Shankar Verma, Pingfu Fu, Gregory T MacLennan, Lee E Ponsky, Chen-Han Wilfred Wu, Jonathan E Shoag, Sanjay Gupta. Distinct immune signature and regulated genes in prostate cancer disparity [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 3617.