Klinik und Poliklinik für Urologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, GB A1, 48149 Münster, Germany.
Anticancer Res. 2013 Dec;33(12):5249-54.
DNA CpG island hypermethylation causes gene silencing and is a common event in prostate carcinogenesis and progression. We investigated its role as a possible prognostic marker in patients with PCA Gleason score ≤7.
We used a quantitative, methylation-specific PCR to analyze methylation patterns at five gene loci (APC, GSTP1, PTGS2, RARbeta and TIG1) in 84 prostate cancer (PCA) tissues (Gleason Score ≤7). Methylation was correlated with established clinico-pathological parameters (preoperative PSA, pathological Gleason score, extraprostatic extension, seminal vesicle penetration, lymph node involvement, surgical margins and age) and PSA recurrence.
DNA hypermethylation was frequently detected at APC (95.2%), GSTP1 (84.5%), PTGS2 (100%), RAR-beta (81.0%) and TIG1 (95.2%). DNA hypermethylation was correlated with Gleason Score (p=0.027; PTGS2) and lymph node involvement (p=0.024; RARbeta). High methylation levels at RARbeta (p=0.023) was a significant predictor of PSA recurrence following radical prostatectomy.
The analysis of DNA hypermethylation provides prognostic information in prognosis of low- and intermediate-grade PCA.
DNA CpG 岛甲基化导致基因沉默,是前列腺癌发生和进展的常见事件。我们研究了其在 Gleason 评分≤7 的 PCA 患者中作为可能的预后标志物的作用。
我们使用定量甲基化特异性 PCR 分析了 84 例前列腺癌(PCA)组织中五个基因座(APC、GSTP1、PTGS2、RARβ和 TIG1)的甲基化模式(Gleason 评分≤7)。甲基化与既定的临床病理参数(术前 PSA、病理 Gleason 评分、前列腺外扩展、精囊侵犯、淋巴结受累、手术切缘和年龄)和 PSA 复发相关。
APC(95.2%)、GSTP1(84.5%)、PTGS2(100%)、RAR-β(81.0%)和 TIG1(95.2%)中经常检测到 DNA 高甲基化。DNA 高甲基化与 Gleason 评分(p=0.027;PTGS2)和淋巴结受累(p=0.024;RARβ)相关。RARβ 的高甲基化水平(p=0.023)是前列腺癌根治性手术后 PSA 复发的显著预测因子。
DNA 高甲基化分析为低级别和中级别 PCA 的预后提供了预后信息。