Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, and CPO-Piemonte, Turin, Italy.
PLoS One. 2013 Jul 9;8(7):e68162. doi: 10.1371/journal.pone.0068162. Print 2013.
Markers that can discriminate between indolent and aggressive prostate tumours are needed. We studied gene methylation in non-neoplastic tissue adjacent to prostate tumour (NTAT) in association with prostate cancer mortality.
From two cohorts of consecutive prostate cancer patients diagnosed at one pathology ward in Turin, Italy, we selected 157 patients with available NTAT and followed them up for more than 14 years. We obtained DNA from NTAT in paraffin-embedded prostate tumour tissues and used probe real-time PCR to analyse methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis coli (APC) gene promoters.
Prevalence of APC and GSTP1 methylation in the NTAT was between 40 and 45%. It was associated with methylation in prostate tumour tissue for the same two genes as well as with a high Gleason score. The hazard ratio (HR) of prostate cancer mortality was 2.38 (95% confidence interval: 1.23-4.61) for APC methylation, and 2.92 (1.49-5.74) for GSTP1 methylation in NTAT. It changed to 1.91 (1.03-3.56) and 1.60 (0.80-3.19) after adjusting for Gleason score and methylation in prostate tumour tissue. Comparison of 2 vs. 0 methylated genes in NTAT revealed a HR of 4.30 (2.00-9.22), which decreased to 2.40 (1.15-5.01) after adjustment. Results were stronger in the first 5 years of follow-up (adjusted HR: 3.29, 95% CI: 1.27-8.52).
Changes in gene methylation are an early event in prostate carcinogenesis and may play a role in cancer progression. Gene methylation in NTAT is a possible prognostic marker to be evaluated in clinical studies.
需要能够区分惰性和侵袭性前列腺肿瘤的标志物。我们研究了与前列腺癌死亡率相关的肿瘤旁非肿瘤组织（NTAT）中的基因甲基化。
我们从意大利都灵一个病理病房连续诊断的两个前列腺癌患者队列中选择了 157 名具有可用 NTAT 的患者，并对其进行了超过 14 年的随访。我们从石蜡包埋的前列腺肿瘤组织中提取 NTAT 的 DNA，并使用探针实时 PCR 分析谷胱甘肽 S-转移酶（GSTP1）和腺瘤性结肠息肉病（APC）基因启动子的甲基化。
NTAT 中 APC 和 GSTP1 甲基化的患病率在 40%至 45%之间。它与前列腺肿瘤组织中相同的两个基因的甲基化以及高 Gleason 评分相关。APC 甲基化的前列腺癌死亡率的危险比（HR）为 2.38（95%置信区间：1.23-4.61），GSTP1 甲基化的 HR 为 2.92（1.49-5.74）。在调整 Gleason 评分和前列腺肿瘤组织中的甲基化后，其分别变为 1.91（1.03-3.56）和 1.60（0.80-3.19）。在 NTAT 中比较 2 个与 0 个甲基化基因，发现 HR 为 4.30（2.00-9.22），调整后降低至 2.40（1.15-5.01）。在随访的前 5 年中，结果更强（调整后的 HR：3.29，95%CI：1.27-8.52）。
基因甲基化的变化是前列腺癌发生的早期事件，可能在癌症进展中起作用。NTAT 中的基因甲基化可能是一种有待在临床研究中评估的预后标志物。
