DNA methylation patterns of ulcer-healing genes associated with the normal gastric mucosa of gastric cancers

J Korean Med Sci. 2010 Mar;25(3):405-17. doi: 10.3346/jkms.2010.25.3.405. Epub 2010 Feb 17.

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.

Keywords: DNA Methylation; Neoplasms; Non-Invasive Cancer; Stomach; Ulcer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • 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
  • PPAR gamma / genetics
  • Peptides / 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*

Substances

  • Antigens, CD
  • Biomarkers
  • CDH1 protein, human
  • Cadherins
  • Growth Substances
  • PPAR gamma
  • Peptides
  • TFF1 protein, human
  • TFF2 protein, human
  • Trefoil Factor-1
  • Trefoil Factor-2
  • Tumor Suppressor Proteins