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Background <p>Prostate-specific antigen (PSA) recurrence after radical prostatectomy signifies increased risk of metastasis and death from prostate cancer. Traditional clinical metrics may not accurately capture the underlying biological heterogeneity of the tumour, which might be improved by consideration of epigenetic biomarkers.</p> Methods <p>This study included 293 Australian participants with prostate cancer treated with radical prostatectomy (mean age: 64 years, Gleason score ≥7: 91%). Fourteen tumour DNA methylation-based signatures of aggressiveness and cell division were calculated. The association of epigenetic signatures with clinical variables were assessed using linear regression and risk ratios for PSA recurrence were assessed using modified Poisson regression.</p> Results <p>Most epigenetic signatures were strongly associated with age, Gleason score, and tumour stage but not with serum PSA levels at diagnosis. Associations were also found with risk of PSA recurrence, with increased risks ranging from 1% to 17% per SD for signatures of clinical variables and 17% to 33% for cell division scores, after adjusting for the main clinicopathological variables. The strongest association was observed for the cell division score <i>RepliTali</i>.</p> Conclusion <p>Prostate cancer tissue DNA methylation-based signatures of aggressiveness and cell division were associated with elevated risk of PSA recurrence, independently of age and traditional clinicopathological variables.</p>

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Tumour-based epigenetic signatures as markers of prostate cancer aggressiveness after radical prostatectomy

  • 期刊论文

  • 发表日期：

    2025年11月20日

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  • Yiyue Zhu,
  • Elaheh Zarean,
  • Danmeng L. Li,
  • Robert L. O’Reilly,
  • Ian D. Davis,
  • Renea A. Taylor,
  • Arun A. Azad,
  • Damien M. Bolton,
  • Nathan Papa,
  • Nathan Lawrentschuk,
  • Robert J. MacInnis,
  • Roger L. Milne,
  • Graham G. Giles,
  • Melissa C. Southey,
  • Pierre-Antoine Dugué

摘要

Background

Prostate-specific antigen (PSA) recurrence after radical prostatectomy signifies increased risk of metastasis and death from prostate cancer. Traditional clinical metrics may not accurately capture the underlying biological heterogeneity of the tumour, which might be improved by consideration of epigenetic biomarkers.

Methods

This study included 293 Australian participants with prostate cancer treated with radical prostatectomy (mean age: 64 years, Gleason score ≥7: 91%). Fourteen tumour DNA methylation-based signatures of aggressiveness and cell division were calculated. The association of epigenetic signatures with clinical variables were assessed using linear regression and risk ratios for PSA recurrence were assessed using modified Poisson regression.

Results

Most epigenetic signatures were strongly associated with age, Gleason score, and tumour stage but not with serum PSA levels at diagnosis. Associations were also found with risk of PSA recurrence, with increased risks ranging from 1% to 17% per SD for signatures of clinical variables and 17% to 33% for cell division scores, after adjusting for the main clinicopathological variables. The strongest association was observed for the cell division score RepliTali.

Conclusion

Prostate cancer tissue DNA methylation-based signatures of aggressiveness and cell division were associated with elevated risk of PSA recurrence, independently of age and traditional clinicopathological variables.