DNA Methylation Patterns of Ulcer-Healing Genes Associated with the Normal Gastric Mucosa of Gastric Cancers

• Published in: Journal of Korean medical science Vol. 25; no. 3; pp. 405 - 417
• Main Authors: Hong, Seung-Jin, Oh, Jung-Hwan, Jung, Yu-Chae, Kim, Young-Ho, Kim, Sung-Ja, Kang, Seok-Jin, Seo, Eun-Joo, Choi, Sang-Wook, Kang, Moo-Il, Rhyu, Mun-Gan
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Academy of Medical Sciences 01.03.2010; 대한의학회
• Subjects: Biomarkers - metabolism; Cadherins - genetics; CpG Islands; DNA Methylation; Female; Gastric Mucosa - pathology; Gastric Mucosa - physiology; Gene Expression Regulation, Neoplastic; Growth Substances - genetics; Humans; Male; Middle Aged; Neoplasm Invasiveness; Original; Peptides - genetics; PPAR gamma - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach Ulcer - genetics; Stomach Ulcer - pathology; Trefoil Factor-1; Trefoil Factor-2; Tumor Suppressor Proteins - genetics; Wound Healing - genetics; 의학일반; Stomach; Non-Invasive Cancer; Ulcer; DNA Methylation; Neoplasms
• ISSN: 1011-8934; 1598-6357; 1598-6357
• DOI: 10.3346/jkms.2010.25.3.405

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 (> or =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.