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

Area of Science:

• Epigenetics
• Cancer Biology
• Genomics

Background:

• Puerto Rican (PR) Hispanic/Latino (H/L) men exhibit the highest prostate cancer (PCa) specific mortality among Hispanic populations.
• The underlying reasons for this disparity, particularly the role of epigenetic modifications in aggressive PCa, remain understudied.

Purpose of the Study:

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

Main Methods:

• Sequencing analysis of 5hmC-enriched DNA from 22 prostate tumors and 24 adjacent normal FFPE samples.
• Identification of differentially methylated genes (DMGs) and pathway analysis.
• Correlation of DMGs with TCGA PCa gene expression data and survival analysis.

Main Results:

• Identified 808 differentially methylated genes (DMGs) in tumors versus normal tissues, with the DNA repair pathway being significantly upregulated.
• Found 59 DMGs with concordant epigenetic and gene expression changes.
• Identified six specific genes (CCDC122, NUDT15, PVT1, RPL30, TRMT12, UBR5) with aberrant 5hmC and gene expression changes associated with progression-free survival.

Conclusions:

• Aberrant 5hmC patterns are associated with aggressive PCa in Puerto Rican men.
• Specific genes show concordant epigenetic and transcriptomic alterations linked to PCa aggressiveness and survival.
• Further research into these epigenetic modifications could inform targeted therapies for high-risk populations.