Glutathione-S-Transferase p 1 Gene Promoter Methylation in Cell-Free DNA as a Diagnostic and Prognostic Tool for Prostate Cancer: A Systematic Review and Meta-Analysis

Abstract

Background. Promoter methylation of glutathione-S-transferase $p1$ (GSTP1) is related to the occurrence of prostate cancer (PCa), but reports are inconsistent about the accuracy of GSTP1 promoter methylation in PCa diagnosis and prognosis. Therefore, we systematically evaluated the diagnostic and prognostic value of GSTP1 promoter methylation in PCa. Methods. The PubMed, EMBASE, Web of Science, and PMC databases were searched for all relevant studies from the date of inception to November 31, 2021. We compared differences in the incidence of GSTP1 promoter methylation in cfDNA between prostate cancer patients and controls. The odds ratio (OR) and hazard ratio (HR) were used as effect sizes, and the result of each effect size is expressed as a 95% confidence interval (95% CI). Results. Our meta-analysis showed that the combined sensitivity and specificity of GSTP1 promoter methylation in cfDNA for the diagnosis of prostate cancer were 0.37 (95% CI = 0.23, 0.53) and 0.97 (95% CI = 0.88, 0.99), respectively. The area under the curve (AUC) with 95% CI was 0.78 (95% CI = 0.75, 0.82). For prognostic variables, hypermethylation of GSTP1 was associated with shorter survival in PCa (HR = 2.57, 95% CI = 1.30, 5.10), with statistical significance in between-study heterogeneity (I2 = 72%, $P=0.006$ ). The results of the subgroup analysis indicated that the heterogeneity of studies may be due to differences in the observed indicators. Conclusions. The results of the meta-analysis substantiate the high specificity of promoter methylation of GSTP1 in cfDNA for the diagnosis of prostate cancer, and it may be used to more precisely evaluate the prognosis of patients with prostate cancer. It may be helpful for the early detection of prostate cancer, but it still must be combined with traditional prostate-specific antigen (PSA) or other methylated genes to accomplish this goal.