Investigating the prognostic utility of promoter methylation in prostate cancer.

OBJECTIVES

We aim to determine the prognostic significance of DNA methylation () in two independent prostate cancer cohorts with long-term clinical follow-up data.

SUBJECTS/PATIENTS AND METHODS: We first re-examined a published, in-house whole genome bisulphite sequencing (WGBS) prostate cancer dataset, derived from radical prostatectomy (RP) tissue ( = 15) with median follow-up 19.5 years, to confirm and visualise the association between and patient mortality. To validate prognostic significance, we used a quantitative methylation-specific head-loop (MS-HL) assay to measure levels in a larger, independent cohort ( = 186), and performed univariable and multivariable Cox survival analysis.

RESULTS

Re-analysis of WGBS data showed a significant increase in in RP samples from patients with lethal versus non-lethal disease. Subsequent analysis in the larger cohort using the MS-HL assay confirmed that was detectable in 97% of RP samples, validating the diagnostic potential of . Univariable Cox survival analysis revealed a significant association between levels and biochemical recurrence and metastatic relapse free survival, with a near-significant association with prostate cancer specific mortality. Notably, multivariable Cox models demonstrated that did not add independent prognostic value beyond standard clinicopathological features.

CONCLUSION

Our study supports the importance of DNA methylation as a tissue-based prostate tumour biomarker. methylation is well established as a diagnostic marker, and in this study, we find that methylation levels are also associated with disease prognosis. Further research is required into the clinical utility of prognostic methylation markers and their functional role in disease progression.