5hmC-profiles in Puerto Rican Hispanic/Latino men with aggressive prostate cancer

Area of Science:

• Epigenetics
• Genomics
• Oncology

Background:

• Puerto Rican (PR) Hispanic/Latino (H/L) men exhibit the highest prostate cancer (PCa) mortality among Hispanic populations.
• The underlying molecular mechanisms, particularly epigenetic alterations, contributing to aggressive PCa in this demographic remain largely unknown.

Purpose of the Study:

• To identify key 5-hydroxymethylcytosine (5hmC) epigenetic modifications in aggressive PCa within PR H/L men.
• To correlate these epigenetic changes with gene expression and PCa aggressiveness.

Main Methods:

• Sequencing analysis of 5hmC-enriched DNA from 22 prostate tumors and 24 adjacent normal FFPE samples from PR H/L men.
• Differential methylation analysis to identify key genes (DMGs).
• Correlation analysis with TCGA PCa gene expression data and survival data.

Main Results:

• Identified 808 differentially methylated genes (DMGs) in tumors, indicating altered Androgen Receptor (AR) regulation, Wnt/β-catenin pathway activation, and downregulated tumor suppressors.
• Found 59 DMGs with concordant epigenetic and gene expression changes, and 111 aggressiveness-related DMGs.
• Highlighted six specific genes (CCDC122, NUDT15, PVT1, RPL30, TRMT12, UBR5) with aberrant 5hmC and gene expression changes associated with progression-free survival.

Conclusions:

• Aberrant 5hmC modifications and associated gene expression changes in specific genes may contribute to the high PCa-specific mortality observed in PR H/L men.
• The identified DMGs and specific gene alterations offer potential biomarkers or therapeutic targets for personalized treatment strategies in this high-risk population.
• Further molecular analyses and validation in larger cohorts are warranted to elucidate the role of these genes in PCa progression and mortality.