Methylation markers for prostate cancer prognosis: a systematic review

We conducted a systematic review to summarize current evidence on the prognostic utility of DNA methylation markers in prostate cancer and ascertain knowledge gaps to inform future research. We identified relevant studies using combined key search against PubMed database. Inclusion criteria were studies of human subjects that examined the association between DNA methylation markers and prostate cancer disease outcomes. The methodological quality of each study was systematically evaluated. Findings were qualitatively summarized. Due to heterogeneity and concerns of internal validity, no meta-analysis was performed. Twenty studies were reviewed; sample size ranged from 35 to 605 men in the prognostic analyses. Sixteen studies examined methylation markers in prostate cancer tissue and four examined circulating DNA methylation markers. Of all genes reviewed, paired-like homeodomain transcription factor 2 (PITX2) methylation was examined in two more rigorously designed studies and was found to be associated with biochemical recurrence. Common limitations in current literature included small sample sizes, lack of adequate adjustment for established prognostic factors, and poor reporting quality. Evidence on the prognostic utility of methylation markers in prostate cancer is inconclusive. Future research should ascertain large samples with adequate follow-up and include patients of racial/ethnic minority and those treated with modalities other than prostatectomy (e.g., using prostate cancer diagnostic biopsy as tissue source).