Korean J Urol.  2012 Mar;53(3):200-205.

DNA Methylation of GSTP1 in Human Prostate Tissues: Pyrosequencing Analysis

• Yoon HY
• Kim YW
• Kang HW
• Kim WT
• Yun SJ
• Lee SC
• Kim WJ
• Kim YJ

Abstract

PURPOSE
DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumor initiation and progression. Differences in methylation patterns between neoplastic and normal cells can be used to detect the presence of cancer. The aim of the present study was to evaluate the usefulness of glutathione-S-transferase-Pi (GSTP1) hypermethylation in discriminating between normal and prostate cancer (PCa) cells and in predicting tumor characteristics by use of quantitative pyrosequencing analysis.
MATERIALS AND METHODS
A total of 100 human prostate tissues obtained from our institute were used in this study: 45 for benign prostatic hyperplasia (BPH) and 55 for PCa. The methylation level of GSTP1 was examined by a quantitative pyrosequencing analysis. The associations between GSTP1 methylation level and clinico-pathological parameter were also compared.
RESULTS
The level of GSTP1 methylation was significantly higher in PCa samples than in BPH samples (56.7+/-32.7% vs. 1.6+/-2.2%, p<0.001). The sensitivity and specificity of GSTP1 methylation status in discriminating between PCa and BPH reached 85.5% and 100%, respectively. Even after stratification by stage, Gleason score, and prostate-specific antigen (PSA) level, similar results were obtained. A positive correlation between GSTP1 methylation level and serum PSA level was observed (r=0.303, p=0.002). There were no associations between GSTP1 methylation level and age, Gleason score, and staging.
CONCLUSIONS
Our study demonstrates that GSTP1 methylation is associated with the presence of PCa and PSA levels. This methylation marker is a potentially useful indicator for the detection and monitoring of PCa.

Keyword

GSTP1; Methylation; Neoplasms; Prostate

MeSH Terms

DNA
DNA Methylation
Epigenomics
Humans
Methylation
Neoplasm Grading
Passive Cutaneous Anaphylaxis
Prostate
Prostate-Specific Antigen
Prostatic Hyperplasia
Prostatic Neoplasms
Sensitivity and Specificity
DNA
Prostate-Specific Antigen

Figure

• 

  FIG. 1 An example of GSTP1 pyrograms in benign prostatic hyperplasia (A) and prostate cancer (B) patients. Pyrogram includes 7 CpG sites and methylation rates. The methylation level of GSTP1 is expressed as a mean.

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  FIG. 2 (A) GSTP1 methylation level in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) patients. Differences (p-value) between BPH and PCa patients were obtained by two-sample t-test. The y axis indicates the absolute methylation expression level of GSTP1. (B) Receiver operator characteristic (ROC) curve analysis of GSTP1 methylation for PCa prediction.

• 

  FIG. 3 GSTP1 methylation level according the prostate-specific antigen (PSA) level. Differences (p-value) among groups were calculated by analysis of variance trend analyses. The y axis indicates the absolute methylation expression level of GSTP1.

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