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<p>DNA methylation, a major epigenetic event associated with prostate cancer (PCa) progression, has been suggested to be influenced by the lipid microenvironment. We aimed to analyze the link between DNA methylation in PCa tissues and the lipid composition of peri-prostatic adipose tissue (PPAT), together with markers of PCa aggressiveness. Global DNA and gene-specific methylation events were evaluated using qMSRE analyses and immunohistochemistry, in cancer tissues from 75 patients treated by prostatectomy for PCa, together with the characterization of the lipid composition of PPAT. The effects of fatty acids (FA) on DNA methylation were measured in PCa cell lines. High 5mC levels correlated with features of PCa aggressiveness. 5hmC levels were associated with cholesterol content in PPAT, and <i>PD-L1</i> methylation was positively linked to linoleic acid content. Moreover, decreased 5mC level and low <i>GSTP1</i> methylation were associated with high n-3 FA content in PPAT. Cell lines experiments suggested a causal relationship between FA exposure and methylation events, mediated by DNMT recruitment. We identified a link between lipid content in PPAT and methylation events in PCa tissues, supported by cell lines experiments, that suggest that FA could influence PCa aggressiveness.</p>

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The DNA methylation landscape of prostate cancer is associated with the lipid composition of periprostatic adipose tissue

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Dorian Espi-Bastien,
  • Nathanael Fort,
  • Cyrille Guimaraes,
  • Arulraj Nadaradjane,
  • Frank Bruyere,
  • Christophe Vandier,
  • Pierre-Francois Cartron,
  • Gaelle Fromont

摘要

DNA methylation, a major epigenetic event associated with prostate cancer (PCa) progression, has been suggested to be influenced by the lipid microenvironment. We aimed to analyze the link between DNA methylation in PCa tissues and the lipid composition of peri-prostatic adipose tissue (PPAT), together with markers of PCa aggressiveness. Global DNA and gene-specific methylation events were evaluated using qMSRE analyses and immunohistochemistry, in cancer tissues from 75 patients treated by prostatectomy for PCa, together with the characterization of the lipid composition of PPAT. The effects of fatty acids (FA) on DNA methylation were measured in PCa cell lines. High 5mC levels correlated with features of PCa aggressiveness. 5hmC levels were associated with cholesterol content in PPAT, and PD-L1 methylation was positively linked to linoleic acid content. Moreover, decreased 5mC level and low GSTP1 methylation were associated with high n-3 FA content in PPAT. Cell lines experiments suggested a causal relationship between FA exposure and methylation events, mediated by DNMT recruitment. We identified a link between lipid content in PPAT and methylation events in PCa tissues, supported by cell lines experiments, that suggest that FA could influence PCa aggressiveness.