Helicobacter pylori-induced modulation of the promoter methylation of Wnt antagonist genes in gastric carcinogenesis

Abstract

Introduction: This study aimed to investigate the changes in the promoter methylation and gene expression of multiple Wnt antagonists between the chronic infection and eradication of Helicobacter pylori (H. pylori) in the gastric carcinogenesis. Methods: The levels of methylation and corresponding mRNA expression of seven Wnt antagonist genes (SFRP1, 2, 5, DKK1, 2, 3, and WIF1) were compared among the patients with H. pylori-positive gastric cancers (GCs), H. pylori-positive and -negative controls by quantitative MethyLight assay and real-time RT PCR, respectively. The changes of the methylation and expression levels of the genes were also compared between the H. pylori eradication and persistent groups 1 year after endoscopic resection of GCs. Results: The methylation levels of SFRP and DKK family genes were significantly increased in the patients with H. pylori-positive GCs and followed by H. pylori-positive controls compared with H. pylori-negative controls (P < 0.001). The SFRP1, 2, and DKK3 gene expression were stepwise down-regulated from H. pylori-negative controls, H. pylori-positive controls and to H. pylori-posiiitive GCs (P < 0.05). Among the Wnt antagonists, only the degrees of methylation and down-regulation of DKK3 were significantly reduced after H. pylori eradication (P < 0.05). Conclusions: Epigenetic silencing of SFRP and DKK family genes may facilitate the formation of epigenetic field during H. pylori-associated gastric carcinogenesis. The epigenetic field may not be reversed even after H. pylori eradication except for DKK3 methylation.