# DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis

## TL;DR

This study finds that DNA methylation patterns in normal-appearing prostate tissue are linked to cancer recurrence and metastasis, suggesting potential new biomarkers for aggressive prostate cancer.

## Contribution

The study identifies DNA methylation sites in normal and cancerous prostate tissue associated with cancer aggressiveness, offering novel insights into early biomarker development.

## Key findings

- Differentially methylated CpGs were found in normal, adjacent normal, and cancer tissues linked to recurrence and metastasis.
- These CpG sites were enriched in promoter and transcription factor binding regions, indicating a role in gene regulation.
- Low intrapatient heterogeneity in methylation patterns supports their potential as reliable biomarkers.

## Abstract

There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-up. We used several samples from each patient including both normal and cancer tissue to study DNA methylation patterns in relation to aggressiveness measured by follow-up data of biochemical recurrence and metastasis status as clinical endpoints. We identified differentially methylated CpGs associated with recurrence and metastasis, regardless of whether the tissue was normal, cancer-adjacent normal, or cancer. The identified CpG sites were over-represented in promoter regions and transcription factor binding regions, suggesting their influence on gene expression regulation. They further exhibited low intrapatient heterogeneity both between normal, normal adjacent, and cancer tissue, making them favorable as potential biomarkers for aggressive prostate cancer. However, validation of a subset of these CpGs in an external dataset was unsuccessful.

The online version contains supplementary material available at 10.1186/s13148-025-01932-x.