title: DNA methylation patterns of ulcer-healing genes associated with the normal gastric mucosa of gastric cancers.
abstract: 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.
authors.affiliation: Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Yu-Chae
authors.initials: YC
authors.lastname: Jung
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Sung-Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seok-Jin
authors.initials: SJ
authors.lastname: Kang
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Seo
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Choi
authors.forename: Moo-Il
authors.initials: MI
authors.lastname: Kang
authors.forename: Mun-Gan
authors.initials: MG
authors.lastname: Rhyu
mesh_terms: D015703:Antigens, CD; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000235:genetics; D010455:Peptides / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D013276:Stomach Ulcer / Q000235:genetics / Q000473:pathology; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C513384:CDH1 protein, human; D015820:Cadherins; D006133:Growth Substances; D047495:PPAR gamma; D010455:Peptides; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins