Preoperative Serum DNA GSTP1 CpG Island Hypermethylation and the Risk of Early Prostate-Specific Antigen Recurrence Following Radical Prostatectomy

Abstract

Purpose: Hypermethylation of the CpG island at the promoter region of the P-class glutathione S-transferase gene (GSTP1) is the most common somatic genome abnormality in human prostate cancer. We evaluated circulating cell-free DNA GSTP1 CpG island hypermethylation as a prognostic biomarker in the serum of men with prostate cancer. Experimental Design: Prostate cancer DNA GSTP1 CpG island hypermethylation was detected using a restriction endonuclease quantitative PCR technique. We analyzed preoperative serum from 85 men with clinically localized prostate cancer treated with radical prostatectomy and from 35 men with a negative prostate biopsy. We then assayed preoperative serum from a data set of 55 pairs of men with clinically localized prostate cancer treated with radical prostatectomy, matched for Gleason score, comprising 55 men suffering prostate-specific antigen (PSA) recurrence (median, 2 years) and 55 men who were free of disease at last follow-up (median, 3 years). The association of serum GSTP1 CpG island hypermethylation and PSA recurrence was determined. Results: Circulating cell-free DNA with GSTP1 CpG island hypermethylation was not detected in the serum of men with a negative prostate biopsy but was detected in 12% of men with clinically localized disease and 28% of men with metastatic cancer (P = 0.003). In the matched data set, eight men (15%) who developed PSA recurrence were positive for DNA with GSTP1 CpG hypermethylation, whereas no patient who was free of disease was positive for GSTP1 CpG island hypermethylation (McNemar test, m 2 = 6.1, P = 0.01). In a multivariable analysis that accounted for recognized prognostic factors, the presence of serum DNA with GTSP1 CpG island hypermethylation was the most significant predictor of PSA recurrence (hazard ratio, 4.4; 95% confidence interval, 2.2, 8.8; P < 0.001).Conclusion: Our study suggests that GSTP1 CpG island hypermethylation may be an important DNA-based prognostic serum biomarker for prostate cancer.

CpG Island hypermethylation in cell‐free serum DNA identifies patients with localized prostate cancer

“…Our hypermethylation frequency of GSTP1 was somewhat higher than those reported by other groups [12][13][14][15]18]. These differences maybe explained by different detection methods and/or differences in the study cohort: Bastian et al used also a restriction endonuclease method and detected GSTP1 hypermethylation in 12% of serum samples from PCA patients in a screening cohort with US-Americans.…”

CpG Island Hypermethylation Profile in the Serum of Men With Clinically Localized and Hormone Refractory Metastatic Prostate Cancer

“…5 In that study we observed that CpG island hypermethylation at GSTP1 predicted early PSA recurrence following radical prostatectomy. Of all men with clinically localized disease those with a positive test for DNA GSTP1 CpG island hypermethylation were at 4.4 times greater risk for biochemical relapse than those with a negative test.…”

“…The results of GSTP1 hypermethylation were included from our previous investigation. 5 The percent of patients with DNA hypermethylation were compared in each group. Because the 4 groups represented worsening disease categories, the percent with DNA hypermethylation was evaluated for a linear trend, ie whether the percent that was methylated increased with each worsening category.…”

DNA Methylation Markers for Prostate Cancer with a Stem Cell Twist

“…A limitation of the Ibragimova et al study is its lack of testing in body fluids (plasma and/or urine), where detection of CpG island hypermethylation could have a clear clinical value (14) and would add to the novelty of the findings. It also would be important to extend the number of specimens in the tissue validation set to ascertain whether all PIN lesions indeed are unmethylated at the TACSTD2 promoter.…”