Bastian Patrick J, Ellinger Jörg, Wellmann Axel, Wernert Nicolas, Heukamp Lukas C, Müller Stefan C, von Ruecker Alexander
Klinik und Poliklinik für Urologie and Institut für Pathologie, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhelms Universität Bonn, Bonn, Germany.
Clin Cancer Res. 2005 Jun 1;11(11):4097-106. doi: 10.1158/1078-0432.CCR-04-1832.
Our study was designed to evaluate promoter CpG island hypermethylation in the diagnosis and prognosis of prostate cancer.
Primary prostate cancers from 53 patients, pelvic lymph nodes, noncancerous prostate tissues, and prostate cell lines were analyzed. Real-time methylation-specific PCR was used to identify CpG island hypermethylation at five promising gene loci (i.e., GSTP1, APC, PTGS2, MDR1, and RASSF1a).
At three gene loci (GSTP1, APC, and PTGS1) and CpG island, hypermethylation was highly prevalent in prostate cancers (71-91%), and analysis of receiver operator curves showed that hypermethylation at these three gene loci can distinguish between prostate cancer and noncancerous prostatic tissue (i.e., benign hyperplasia) with a sensitivity of 71.1% to 96.2% and a specificity of 92.9% to 100%. Using sensitive SYBR green methylation-specific PCR technology, we observed a respective 28% and 71% hypermethylation rate at the RASSF1a and MDR1 loci in benign prostate hyperplasia, which may represent early nonaggressive carcinogenesis. Methylation characteristics in prostate cancer metastases (i.e., pelvic lymph nodes) were comparable to the respective primary cancer. Statistical analysis showed no correlation between the methylation status of a single gene locus and clinicopathologic variables (e.g., preoperative prostate specific antigen levels, Gleason score, capsular penetration, involvement of seminal vesicle, and age). In contrast, the methylation of two (GSTP1/APC; GSTP1/PTGS2) or three (GSTP1/APC/PTGS2) gene loci correlated with prognostic indicators (i.e., pathologic stage, extraprostatic extension, and Gleason score, but not with prostate specific antigen levels).
Our data suggest that the evaluation of DNA hypermethylation at three gene loci (i.e., GSTP1, APC, and PTGS2) is of diagnostic and prognostic value in prostate cancer.
本研究旨在评估启动子CpG岛高甲基化在前列腺癌诊断和预后中的作用。
分析了53例患者的原发性前列腺癌、盆腔淋巴结、非癌性前列腺组织和前列腺细胞系。采用实时甲基化特异性PCR技术检测5个有前景的基因位点（即GSTP1、APC、PTGS2、MDR1和RASSF1a）的CpG岛高甲基化情况。
在三个基因位点（GSTP1、APC和PTGS1）及其CpG岛，高甲基化在前列腺癌中高度普遍（71%-91%），受试者操作曲线分析表明，这三个基因位点的高甲基化可区分前列腺癌和非癌性前列腺组织（即良性增生），灵敏度为71.1%至96.2%，特异性为92.9%至100%。使用灵敏的SYBR Green甲基化特异性PCR技术，我们观察到良性前列腺增生中RASSF1a和MDR1位点的高甲基化率分别为28%和71%，这可能代表早期非侵袭性癌变。前列腺癌转移灶（即盆腔淋巴结）中的甲基化特征与相应的原发性癌相似。统计分析表明，单个基因位点的甲基化状态与临床病理变量（如术前前列腺特异性抗原水平、Gleason评分、包膜侵犯、精囊受累和年龄）之间无相关性。相反，两个（GSTP1/APC；GSTP1/PTGS2）或三个（GSTP1/APC/PTGS2）基因位点的甲基化与预后指标（即病理分期、前列腺外侵犯和Gleason评分，但与前列腺特异性抗原水平无关）相关。
我们的数据表明，评估三个基因位点（即GSTP1、APC和PTGS2）的DNA高甲基化在前列腺癌的诊断和预后中具有重要价值。
