Abstract 1896: Dysregulation of DNA methylation in prostate cancer among African American men
Authors: Berglund Anders , Yamoah Kosj , Osterman Carlos Diaz , Dutil Julie , Matta Jaime , Ruiz-Deya Gilberto , Wang Liang , Park Hyun , Lotan Tamara , Putney Ryan , Kim Sungjune , Kim Seung Joon , Gwede Clement , Falahat Rana , Mule James , Kim Youngchul , Chakrabarti Ratna , Park Jong Y. 
Published: April 2023

Men of African ancestry have the higher incidence and mortality rates of prostate cancer (PCa) worldwide. These health disparities may be contributed by environmental or biological factors, such as epigenomics. Differential DNA methylation can influence carcinogenesis and disease progression. Indeed, the most common molecular event in PCa is dysregulation of DNA methylation. Among these epigenetic changes, some specific changes may be associated with poor outcomes. Numerous studies reported that differential DNA methylation influences the likelihood of developing PCa and affects its progression. However, most studies were based on European American patients. There is a need to investigate methylation profiles to evaluate potential African American-specific methylated genes, since differential DNA methylation may influence health disparities in PCa. This study aimed to investigate differentially DNA methylated genes between tumor vs. adjacent normal, and aggressive vs. indolent PCa (based on Gleason Score) in 120 African American patients from Florida. Genomic DNA samples were extracted by macro-dissection from FFPE. DNA methylation patterns were assessed using the human Illumina Infinium Methylation EPIC array. We identified 5,097 differentially methylated CpG-sites (q&lt;0.01, lΔβl &gt; 0.2) A few representative differentially methylated regions (DMRs) include immune genes, such as CD40, OX40L, Galectin 3, and STING, in prostate tumor tissues as compared with normal tissues. There was also a clear global increase of methylation level in the tumor samples compared to the normal tissues. Regarding PCa aggressiveness, 6,775 (Hypo:4,252, and Hyper: 2,523) differentially methylated CpG-sites (q&lt;0.05, lΔβl &gt; 0.1) were identified when two groups GG1 (Gleason score 6) vs GG4/5 (Gleason score 8≤) were compared. Among these 6,775 CpG-sites, many CpG-probes are consistently significant in more than one comparison. For example, 1,182 hyper and 1,660 hypo-methylation sites were identified in the comparison between GG1 and GG2/3 (Gleason score 7), while 362 hyper- and 1,640 hypo-methylation sites were found in the GG2/3 vs GG4/5 comparison. A small fraction of probes (51 hyper and 155 hypomethylated probes) was consistently found in all comparisons. These genes, MMP16, CDH13, CCND2, and SEPT9, were previously reported to have a role in PCa progression. This study identified several differentially methylated genes, associated with risk or aggressiveness. Most of these changes appear to overlap in different comparisons, thus GG1 vs. GG2/3 or GG2/3 vs. GG4/5 comparison. Many differentially methylated genes identified here have previously been associated with PCa risk or tumor aggressiveness. These results will shed light on potential mechanisms contributing to PCa disparities in African American population.

Citation Format: Anders Berglund, Kosj Yamoah, Carlos Diaz Osterman, Julie Dutil, Jaime Matta, Gilberto Ruiz-Deya, Liang Wang, Hyun Park, Tamara Lotan, Ryan Putney, Sungjune Kim, Seung Joon Kim, Clement Gwede, Rana Falahat, James Mule, Youngchul Kim, Ratna Chakrabarti, Jong Y. Park. Dysregulation of DNA methylation in prostate cancer among African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1896.