Epigenome-Wide DNA Methylation Patterns in Prostate Adenocarcinoma, Benign Hyperplasia, Metastatic Disease, and Related Lifestyle Factors among African American Men [Georgetown ]

ABSTRACT: African American (AA) men have higher prostate cancer (PCa) incidence and mortality rates than any other racial/ethnic group in the USA. Biological differences including aberrant epigenetic DNA methylation changes likely contribute to the PCa disparities. Our study aims to identify differentially methylated CpG sites and genes among histologic localized adenocarcinoma PCa, metastatic PCa (mCRPC), and Benign Prostatic Hyperplasia (BPH) samples. We performed genome-wide DNA methylation profiling in 100 AA prostate tissues using Illumina Methylation EPIC array. Global hypermethylation indicating epigenetic silence was observed in localized adenocarcinoma PCa compared to paired normal and BPH samples. On the other hand, significant hypomethylation suggesting tumor associated activation of oncogenes and chromatin remodeling was observed in mCRPC. Using Shannon entropy as a metric for epigenetic heterogeneity, mCRPC samples exhibited significant elevated entropy, reflecting greater methylation variability than localized adenocarcinoma PCa and BPH. We also identified distinct smoking and alcohol-associated methylation signatures, with specific CpG sites showing significant differential methylation compared to non-exposed patients. Our analysis provides insights into methylation profiles as predictive markers for distinguishing between BPH, PCa and mCRPC that are also influenced by lifestyle factors. More importantly, aberrations in methylation favor PCa aggressiveness to metastasis and genomic instability that implies aging and environmental factors. Overall, the differential methylation patterns suggest potential for patient stratification, biomarker-driven treatment strategies including epigenetic therapeutic strategies for AA PCa.

ORGANISM(S): Homo sapiens

PROVIDER: GSE323379 | GEO | 2026/03/30

REPOSITORIES: GEO