前列腺癌中谷胱甘肽S-转移酶P1基因（GSTP1）启动子区域CpG岛的高甲基化：一种有用的诊断和预后标志物？

Hypermethylation of the CpG islands in the promoter region of the GSTP1 gene in prostate cancer: a useful diagnostic and prognostic marker?

作者信息

Bernardini Sergio, Miano Roberto, Iori Roberta, Finazzi-Agrò Enrico, Palmieri Giampiero, Ballerini Sabrina, Angeloni Caterina, Orlandi Augusto, Bellincampi Lorenza, Cortese Claudio, Federici Giorgio

机构信息

Department of Internal Medicine, Policlinico Tor Vergata, University of Tor Vergata, Rome, Italy.

出版信息

Clin Chim Acta. 2004 Dec;350(1-2):181-8. doi: 10.1016/j.cccn.2004.07.022.

DOI:10.1016/j.cccn.2004.07.022

PMID:15530476

Abstract

BACKGROUND

Recently, many studies have focused on the potential diagnostic value of the promoter hypermethylation of the GSTP1 gene in prostate cancer.

METHOD

A total of 144 patients, undergoing eight-core prostatic biopsies for a clinically suspected prostate cancer, was analyzed. Two different tissue samples were collected from the same area of the prostate and then divided for both genomic DNA extraction and pathological examination. In order to perform molecular analysis, prostatic tissue samples were digested with the methylation-sensitive restriction enzyme HpaII and then amplified by conventional polymerase chain reaction (PCR).

RESULTS

Prostate cancer was diagnosed in 42/144 patients, and promoter hypermethylation of GSTP1 gene was detected in 31/42 of prostate cancer (sensitivity=74%) and in 2/102 of negative specimens (specificity=98%). A significant association between GSTP1 promoter hypermethylation both with a Gleason score >or=7 (Fisher's exact P=0.01) and the presence of Gleason grade 4 and/or grade 5 (Fisher's exact P=0.03) was found.

CONCLUSION

Promoter hypermethylation of the GSTP1 gene is a highly specific--but not a very sensitive--marker of prostate cancer. Our data showed a significant association between the methylation status of the GSTP1 gene and Gleason score and grade, suggesting a potential prognostic value of this epigenetic DNA alteration.

摘要

背景

最近，许多研究聚焦于GSTP1基因启动子高甲基化在前列腺癌中的潜在诊断价值。

方法

对总共144例因临床怀疑前列腺癌而接受八芯前列腺活检的患者进行分析。从前列腺同一区域采集两份不同的组织样本，然后分别用于基因组DNA提取和病理检查。为进行分子分析，前列腺组织样本用甲基化敏感限制酶HpaII消化，然后通过常规聚合酶链反应（PCR）扩增。

结果

144例患者中有42例被诊断为前列腺癌，在42例前列腺癌患者中的31例（敏感性=74%）以及102例阴性样本中的2例（特异性=98%）检测到GSTP1基因启动子高甲基化。发现GSTP1启动子高甲基化与Gleason评分≥7（Fisher精确检验P=0.01）以及存在Gleason 4级和/或5级（Fisher精确检验P=0.03）均有显著关联。