Hypermethylation of multiple Wnt antagonist genes in gastric neoplasia: Is H pylori infection blasting fuse?

Wnt antagonist genes hypermethylation has been found in several tumors. Accordingly, the events that occur during the progression of adenoma to carcinoma have been characterized and include activation of the Wnt-pathway. Further, gastric adenoma (GA) is a premalignant lesion of gastric adenocarcinoma (GAC). In this paper, we focused our interesting on Wnt signaling path function in the pathogenesis of GAC. We compared the differences between low grade adenoma (LGA), high grade adenoma (HGA), GACs and corresponding normal gastric tissue (NGT). Specific indexes include the pathological characteristics of gastric neoplasia, Helicobacter pylori infection, β-catenin mutation status, and methylation status of Wnt antagonist genes. There was significant difference of β-catenin expression in patient with NGT, LGA, HGA, and GAC, the results respectively were 4.2%, 41.7%, 83.3%, and 91.7%. Only 1 GACs was detected exon 3 of β-catenin mutation. Wnt antagonist genes mRNA expression levels, such as APC, sFRP-1, Wif-1, and Dkk-1, were significantly reduced in GAC. Promoter methylation levels of the 4 genes were significantly elevated in GAC and HGA compared to NGT and LGA. However, there was no significant difference between HGAs and GACs. The β-catenin abnormal expression was correlated with hypermethylation of these 4 genes. Multiple gene concurrent methylation phenomenon was increased from NGTs to GACs; the amount of methylation genes in GACs and HGAs was more than NGTs and LGAs. The more methylation of the above-mentioned genes, the more severity of local inflammation. The infection rate of H pylori was significantly higher in patient with HGA (66.7%, 16/24) and GAC (58.5%, 14/24) than in LGAs (16.7%,4/24) (P(HGA-LGA) = .024, P(GAC-LGA) = .032). In addition, the present of H pylori also correlated with the β-catenin abnormal expression and the hypermethylation status of Wnt antagonist genes (P < .001). But other parameters in adenoma cases had no significantly related with infection of H pylori. Hypermethylation of Wnt antagonist genes may have a tight relationship with gastric tumorigenesis. And these genes may increase the incidence of GAC. Additionally, H pylori may have promotion function in GA formation.