DNA Methylation Patterns of Ulcer-Healing Genes Associated with the Normal Gastric Mucosa of Gastric Cancers.
10.3346/jkms.2010.25.3.405
- Author:
Seung Jin HONG
1
;
Jung Hwan OH
;
Yu Chae JUNG
;
Young Ho KIM
;
Sung Ja KIM
;
Seok Jin KANG
;
Eun Joo SEO
;
Sang Wook CHOI
;
Moo Il KANG
;
Mun Gan RHYU
Author Information
1. Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea. rhyumung@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
DNA Methylation;
Stomach;
Ulcer;
Non-Invasive Cancer;
Neoplasms
- MeSH:
Biological Markers/metabolism;
Cadherins/genetics;
CpG Islands;
*DNA Methylation;
Female;
*Gastric Mucosa/pathology/physiology;
Gene Expression Regulation, Neoplastic;
Growth Substances/genetics;
Humans;
Male;
Middle Aged;
Neoplasm Invasiveness;
PPAR gamma/genetics;
Peptides/genetics;
*Stomach Neoplasms/genetics/pathology;
*Stomach Ulcer/genetics/pathology;
Tumor Suppressor Proteins/genetics;
Wound Healing/*genetics
- From:Journal of Korean Medical Science
2010;25(3):405-417
- CountryRepublic of Korea
- Language:English
-
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.
