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

Zhu, Y; Dugu&#233;, PA; Zarean, E; Li, DL; O&#39;Reilly, RL; Davis, ID; Taylor, RA; Azad, AA; Bolton, DM; Papa, N; Lawrentschuk, N; MacInnis, RJ; Milne, RL; Giles, GG; Southey, MC

Author(s): Zhu, Y; Dugué, PA; Zarean, E; Li, DL; O'Reilly, RL; Davis, ID; Taylor, RA; Azad, AA; Bolton, DM; Papa, N; Lawrentschuk, N; MacInnis, RJ; Milne, RL; Giles, GG; Southey, MC;
Details: Publication Year 2026-02,Volume 134,Issue #3,Page 477-485
Journal Title: British Journal of Cancer
Publication Type: Research article
Abstract: 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.
Publisher: Springer Nature
Keywords: Humans; Male; *Prostatic Neoplasms/surgery/genetics/pathology/blood; Prostatectomy; *DNA Methylation; Middle Aged; Aged; *Biomarkers, Tumor/genetics; *Epigenesis, Genetic; *Neoplasm Recurrence, Local/genetics/pathology; Prostate-Specific Antigen/blood; Neoplasm Grading
Department(s): Laboratory Research; Medical Oncology
Publisher's Version: https://doi.org/10.1038/s41416-025-03257-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-12-05 02:49:49

Last Modified: 2026-02-03 06:11:44