Promoter methylation and down-regulation of DAPK is associated with gastric atrophy

Abstract

Promoter methylation of death-associated protein kinase (DAPK) occurs frequently in cancer cells, which results in the decreased transcription of DAPK. Although promoter methylation of DAPK has been previously reported, it has not been explored in the surrounding normal tissues of gastric cancer patients. Herein we have examined whether the promoter methylation of DAPK gene or down-modulation of DAPK is associated with gastric atrophy. Thirty-nine samples of surgically resected gastric carcinomas and corresponding non-tumorous tissues were studied. Methylation-specific polymerase chain reaction was performed to test DAPK promoter methylation. We evaluated the expression level of DAPK protein in normal and atrophic gastric tissue by both Western blot analysis and immunohistochemical staining. Significant correlation was not observed between methylation and an advanced pathological stage of tumor. No association was found between promoter methylation of DAPK and Helicobacter pylori infection, whereas a close association was observed with the presence of gastric atrophy and DAPK promoter methylation (P=0.015). The level of DAPK protein expression was significantly low in atrophic gastritis compared with those without atrophy (P=0.003). Collectively, DAPK promoter methylation and down-regulation is tightly associated with gastric atrophy, which often contributes to the preneoplastic changes in gastric carcinogenesis.