DNA methylation patterns of ulcer-healing genes associated with the normal gastric mucosa of gastric cancers.
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.
Hong
Seung-Jin
SJ
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Oh
Jung-Hwan
JH
Jung
Yu-Chae
YC
Kim
Young-Ho
YH
Kim
Sung-Ja
SJ
Kang
Seok-Jin
SJ
Seo
Eun-Joo
EJ
Choi
Sang-Wook
SW
Kang
Moo-Il
MI
Rhyu
Mun-Gan
MG
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*
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