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Cancer-associated fibroblasts (CAFs) in prostate cancer exhibit unique DNA methylation changes, distinct from nonmalignant cells. These epigenetic alterations in the tumor microenvironment offer potential new diagnostic biomarkers.

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Area of Science:

  • Epigenetics
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • Solid tumor progression involves complex interactions between cancer cells and the surrounding microenvironment.
  • Molecular profiling has predominantly focused on cancer cells, leaving the tumor microenvironment's protumorigenic features largely uncharacterized.

Purpose of the Study:

  • To investigate genome-wide DNA methylation patterns in cancer-associated fibroblasts (CAFs) from localized prostate cancer.
  • To compare the epigenome of CAFs with nonmalignant prostate fibroblasts (NPFs).
  • To identify epigenetic modifications within the tumor microenvironment and their potential as diagnostic biomarkers.

Main Methods:

  • Whole-genome bisulfite sequencing (WGBS) was employed to analyze DNA methylation landscapes.
  • Comparative analysis of methylation profiles between CAFs and NPFs.
  • Correlation of differentially methylated regions with gene expression changes and functional analysis.

Main Results:

  • CAFs from localized prostate cancer display distinct and stable genome-wide DNA methylation changes, particularly at enhancers and promoters, compared to NPFs.
  • Differentially methylated regions in CAFs are associated with cancer-related gene expression functions and can reliably distinguish CAFs from NPFs.
  • A subset of epigenetic modifications is shared between CAFs and prostate cancer epithelial cells, indicating tumor-specific epigenome alterations.

Conclusions:

  • The distinct methylome of CAFs represents a novel epigenetic hallmark of the prostate cancer microenvironment.
  • These findings reveal shared tumor-specific epigenetic modifications across cancer cells and their microenvironment.
  • The identified epigenetic changes in CAFs hold promise for developing new biomarkers for improved diagnostic sample interpretation.