Abstract B037: Predictive ability of a DNA methylation signature for high-grade prostate tumors among African American men

Abstract

Prior studies have identified prostate tumor DNA methylation (DNAm) signatures associated with prostate cancer (PCa) mortality and recurrence. However, despite African American (AA) men being more likely to develop aggressive PCa and have higher rates of mortality, most prior studies have been conducted among European American (EA) men. Here, we assessed the ability of a published DNAm signature (Geybels et al. 2016) developed in The Cancer Genome Atlas (TCGA) among predominantly EA men with PCa to distinguish between high-grade vs. low-grade tumors among African American (AA) men with PCa in Maryland. We conducted a cross-sectional analysis of formalin-fixed, paraffin-embedded prostate tumor tissue from 100 men with PCa who underwent radical prostatectomy at the University of Maryland Medical Center from 1992-2021. Tumor grade (Gleason score) was abstracted from pathology reports. DNAm data was measured with Illumina’s EPIC v2 array yielding 683,742 CpG sites after quality control steps. Of the 52 differentially methylated CpG sites identified using elastic net regression and included in the Geybels et al. 2016 signature, 38 of these CpG sites were available in our dataset after quality control. We assessed the ability of a signature with these 38 CpG sites to discriminate tumors by Gleason score (≤3+4 vs. ≥4+3 and ≤6 vs. ≥4+3) through computing the areas under the curve (AUCs) with 95% confidence intervals (CIs). Of the 100 individuals with PCa, 75 individuals had a Gleason score ≤3+4 (17 of which had a Gleason Score ≤6) and 25 individuals had a Gleason score ≥4+3. The AUC for predicting ≤3+4 vs. ≥4+3 was 0.69 (95% CI: 0.57-0.79) and the AUC for predicting ≤6 vs. ≥4+3 was 0.67 (95% CI: 0.49-0.86). A previous DNAm signature developed among primarily EA men had modest ability to distinguish between high- and low- grade tumors among AA men in our cohort. Future directions include building a novel DNAm signature using elastic net regression in our cohort of 100 AA men and testing the predictive ability of our signature in comparison to previous signatures in a cohort of 121 AA men with PCa diagnosed at the Moffitt Cancer Center in Tampa, FL. Camryn M. Cohen, Yuji Zhang, Teklu B. Legesse, Ashley Johnson, Kimberly Clark, Nicholas Ambulos Jr, Jing Yin, Jong Y. Park, Soren M. Bentzen, Arif Hussain, Joanne Dorgan, Kathryn H. Barry. Predictive ability of a DNA methylation signature for high-grade prostate tumors among African American men [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B037.