DNA Methylation Patterns of Ulcer-Healing Genes Associated with the Normal Gastric Mucosa of Gastric Cancers
DNA Methylation Patterns of Ulcer-Healing Genes Associated with the Normal Gastric Mucosa of Gastric Cancers
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DOI：
10.3346/jkms.2010.25.3.405
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发表时间：
2010-03-01
影响因子：
4.5
通讯作者：
Rhyu, Mun-Gan
中科院分区：
文献类型：
--
作者：
Hong, Seung-Jin;Oh, Jung-Hwan;Rhyu, Mun-Gan
最近的证据表明，胃粘膜损伤会引起 DNA 甲基化的适应性变化。在这项研究中，评估了健康个体和癌症患者正常胃粘膜中关键组织特异性基因的甲基化状态。包括溃疡愈合基因（TFF1、TFF2、CDH1 和 PPARG）在内的 14 个基因的甲基化可变位点选自转录起始位点附近的 CpG 岛边缘或非岛 CpG。通过半定量甲基化特异性聚合酶链反应（PCR）分析检查健康个体以及23例溃疡、21例非浸润性癌症和53例癌症患者的正常胃粘膜。溃疡愈合基因同时与其他基因甲基化，具体取决于健康个体正常粘膜中是否存在 CpG 岛。溃疡患者中 TFF2 和 PPARG 基因经常甲基化不足。过度或中度甲基化的 TFF2 和甲基化不足的 PPARG 基因在 1 期癌症患者 (71%) 中比健康个体（10%；比值比 [OR]，21.9）和非侵袭性癌症患者（21%；OR，8.9）更常见。癌症患者的 TFF2-PPARG 甲基化模式在老年组中更强（>= 55 岁；OR，43.6）。这些结果表明，溃疡愈合基因的组合甲基化模式可作为预测胃粘膜易患癌症的敏感标记。
Recent evidence suggests that gastric mucosal injury induces adaptive changes in DNA methylation. In this study, the methylation status of the key tissue-specific genes in normal gastric mucosa of healthy individuals and cancer patients was evaluated. The methylation-variable sites of 14 genes, including ulcer-healing genes (TFF1, TFF2, CDH1, and PPARG), were chosen from the CpG-island margins or non-island CpGs near the transcription start sites. The healthy individuals as well as the normal gastric mucosa of 23 ulcer, 21 non-invasive cancer, and 53 cancer patients were examined by semiquantitative methylation-specific polymerase chain reaction (PCR) analysis. The ulcer-healing genes were concurrently methylated with other genes depending on the presence or absence of CpG-islands in the normal mucosa of healthy individuals. Both the TFF2 and PPARG genes were frequently undermethylated in ulcer patients. The over-or intermediate-methylated TFF2 and undermethylated PPARG genes was more common in stage-1 cancer patients (71%) than in healthy individuals (10%; odds ratio [OR], 21.9) and non-invasive cancer patients (21%; OR, 8.9). The TFF2-PPARG methylation pattern of cancer patients was stronger in the older-age group (>= 55 yr; OR, 43.6). These results suggest that the combined methylation pattern of ulcer-healing genes serves as a sensitive marker for predicting cancer-prone gastric mucosa.