Abstract PO-227: DNA methylation as a predictor of aggressive prostate cancer in Puerto Rican men

Abstract

Abstract Background: Incidence and mortality rates among Hispanic/Latino (H/L) men with prostate cancer (PCa) are almost same as non-Hispanic whites (NHW) men. However, these data may be over-generalized because all H/L subgroups are aggregated into one broad group. Therefore, few studies focused on health disparity of PCa in H/L men. Data from the Puerto Rico (PR) Cancer Registry shows that in men, PCa is the #1 cancer, both in terms of incidence (39.9% of all cancer cases) and mortality (18.3% of all cancer deaths). Recent studies reported that PR men have a higher rate of poor outcomes than NHW regardless of treatment and also after surgical treatment. Further, PR patients had significantly higher PCa specific mortality than non-Hispanic blacks. Although PCa is normally characterized by a slow progression, ~20-30% of cases are associated with an aggressive phenotype associated with metastasis and death. A key molecular feature of this aggressive phenotype is the dysregulation of DNA repair genes.The objective of this pilot study was to investigate epigenetic differences in tumor DNA methylation, between PR and NHW men to identify specific biomarkers for PCa in PR men. Methods: Archived paraffin-embedded (FFPE) blocks of 24 prostate tumor and 24 adjacent normal tissues were collected through the Puerto Rico Biobank. We selected 12 aggressive and 12 indolent cases based on aggressiveness, mainly based on the Gleason scores and clinical stage. Both 24 tumor and 24 normal tissues were measured methylation level using epigenome wide Illumina EPICDNA methylation platform. Results: DNA methylation analysis showed a clear distinction between tumor and normal tissues. In addition, twenty significant differentially methylated genes associated with aggressive disease were identified including: SLC5A8, FGF12, LCP1, TRH, PFKFB3, and LIN28B Six significantly differentially methylated genes associated with aggressive cases. We also identified 27 DNA repair genes, which were differentially methylated (log2 FC > 0.1)) between aggressive and indolent PR cases. 7genes were hypermethylated and 20 genes were hypomethylated. Multiple DNA repair genes were differentially methylated including ATM, ERCC5, XRCC2, XRCC3, and BRCA1. The ancestry analysis for these men showed a distribution where the European ancestry is the more prevalent (64%) followed by West African ancestry (21%) and Indigenous American ancestry (15%). Although our results have to be validated with large independent samples, for the first time, a few potential DNA methylation biomarkers for PCa progression in PR men were identified. The outcomes of these studies could lead to development of better methods for clinicians to stratify PR men with PCa that have high risk of metatastic and lethal disease with an optimal treatment. The aggressive PCa we are studying may be a cancer disparity in the PR population that has not been identified. Supported by grants #: U54 CA163071-07 and U54 CA163068-07. Citation Format: Gilberto Ruiz-Deya, Jamie Matta, Jarline Encarnacion-Medina, Carmen Ortiz-Sanchez, Liang Wang, Anders Berglund, Youngchul Kim, Jong Park. DNA methylation as a predictor of aggressive prostate cancer in Puerto Rican men [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-227.