Development of diagnostic methods of gastrointestinal cancer using integrated analysis of nuclear molecules

点击翻译按钮获取中文摘要

The molecular mechanism by which H. pylori infection leads to gastric cancer is not fully understood. Similarly, patients with enlarged fold gastritis, one cause of which is H. pylori infection, have an increased risk of gastric cancer, though again molecular mechanism is unclear. In the present study, we analyzed the methylation status of LINE-1 and three cancer-related genes in a panel of gastric mucosae, with or without enlarged fold gastritis. We used bisulfite-pyrosequencing to assess the levels of LINE-1, CDH1, CDH13 and PGP9.5 methylation in 78 gastric mucosa specimens from 48 patients. Levels of LINE-1 methylation were significantly reduced in mucosae from patients with enlarged fold gastritis. This hypomethylation of LINE-1 was associated with increased methylation of the 5' CpG islands of the genes, which suggests that, in enlarged fold gastritis, methylation of the promoter regions of certain genes is accompanied by global demethylation of repetitive sequences. Our results indicate that genome-wide hypomethylation and regional hypermethylation occur in enlarged fold gastritis and may contribute to the tumorigenesis of diffuse type gastric cancers.