Morphologic characterization of residual DNA methylation in the gastric mucosa after Helicobacter pylori eradication

Residual DNA methylation in the gastric mucosa after Helicobacter pylori (H. pylori) eradication may have a role in gastric carcinogenesis. We examined the association between morphologic features and promoter methylation status of non-neoplastic gastric mucosa especially after H. pylori eradication. A total of 140 gastric specimens from 99 participants who had at least 6 months of post-eradication period were examined. The magnifying narrow-band imaging (NBI) endoscopic feature of gastric mucosa was divided into two types: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA, and PRDM5) were examined by bisulfite pyrosequencing. The atrophic type, informative endoscopic features of intestinal metaplasia, demonstrated higher methylation levels in all five genes compared to the restored type (all P < 0.0001). In the restored type, methylation levels were significantly lower among the samples with longer post-eradication period (for all genes, P < 0.0001), which was not observed in atrophic type (for all genes, P > 0.1). Multivariate analysis demonstrated that atrophic type or presence of intestinal held an independent factor for hyper methylation (odds ratio: 24.69, 95% confidence interval: 6.95-87.76, P < 0.0001). The atrophic type by the magnifying NBI and presence of intestinal metaplasia are the morphologic characteristics of residual DNA methylation of after H. pylori eradication, regardless of the post-eradication period and it might be considered as the epigenetic irreversible point with H. pylori eradication.