Measurement of GSTP1 promoter methylation in body fluids may complement PSA screening: a meta-analysis

Abstract

Background:Prostate-specific antigen (PSA) screening has low specificity. Assessment of methylation status in body fluids may complement PSA screening if the test has high specificity.Method:The purpose of this study was to conduct a meta-analysis of the sensitivity and specificity for prostate cancer detection of glutathione-s-transferase–π (GSTP1) methylation in body fluids (plasma, serum, whole blood, urine, ejaculate, and prostatic secretions). We conducted a comprehensive literature search on Medline (Pubmed). We included studies if they met all four of the following criteria: (1) measurement of DNA methylation in body fluids; (2) a case-control or case-only design; (3) publication in an English journal; and (4) adult subjects. Reviewers conducted data extraction independently using a standardised protocol. Twenty-two studies were finally included in this paper. Primer sequences and methylation method in each study were summarised and evaluated using meta-analyses. This paper represents a unique cross-disciplinary approach to molecular epidemiology.Results:The pooled specificity of GSTP1 promoter methylation measured in plasma, serum, and urine samples from negative-biopsy controls was 0.89 (95% CI, 0.80–0.95). Stratified analyses consistently showed a high specificity across different sample types and methylation methods (include both primer sequences and location). The pooled sensitivity was 0.52 (95% CI, 0.40–0.64).Conclusions:The pooled specificity of GSTP1 promoter methylation measures in plasma, serum, and urine was excellent and much higher than the specificity of PSA. The sensitivity of GSTP1 was modest, no higher than that of PSA. These results suggest that measurement of GSTP1 promoter methylation in plasma, serum, or urine samples may complement PSA screening for prostate cancer diagnosis.

Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities

“…A recent meta-analysis of 22 manuscripts indicated good specificity (89%) but modest sensitivity (52%) of GSTP1 differential methylation for PCA screening [81]. The detection of hypermethylated DNA is also an adverse prognostic marker: RASSF1A, RARB2, and GSTP1 hypermethylation were correlated with the Gleason score and the serum PSA [82].…”

APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis

“…The pooled specificity for all included studies was 0.91 (95% CI: 0.82-0.95), and the pooled sensitivity was 0.78 (95% CI: 0.63-0.88). For the traditional biomarker, the sensitivity of PSA varied, but the specificity was generally low at about 20%, 32,54 which suggested that the APC methylation test has a much higher specificity than the PSA test. There was no evidence of publication bias (P ¼ 0.33).…”

“…All data used a log-odds scale (eg, for specificities, the effect size used was log (Spec/(1-Spec)). 32 Finally, due to the heterogeneity between studies, we performed the Cochrane Q test of heterogeneity for each analysis (based on deviations of observed log-odds from the common log-odds). The analyses were conducted using Stata 9.0 (Stata Corporation, College Station, TX, USA), and all P-values were two-tailed.…”

Key pathways involved in prostate cancer based on gene set enrichment analysis and meta analysis

“…In the finding genes of this pathway, CYP3A4 and CYP3A5 expression is related to androgen metabolism (Rebbeck et al, 2008). Meta-analysis studies show that measurement of GSTP1 promoter methylation in plasma, serum, or urine samples may complement PSA screening for prostate cancer diagnosis (Wu et al, 2011).…”