A comparative study on promoter DNA methylation status of the CDO1 tumor suppressor gene in chronic gastritis and gastric cancer: The role of Helicobacter pylori infection
Silencing of the Cysteine dioxygenase-1 (CDO1) tumor suppressor gene by aberrant DNA methylation contributes to gastric carcinogenesis. Despite earlier data indicating that Helicobacter pylori (H. pylori) infection induces aberrant DNA methylation in the gastric mucosa, the CDO1 methylation level has not been studied in H. pylori-positive (HPP) patients with chronic gastritis. This study aimed to investigate the CDO1 methylation level in patients with chronic gastritis who have and do not have H. pylori infection, in comparison to gastric tumours. The quantitative analysis of the promoter methylation of the CDO1 gene and CDO1 immunopositivity was determined in 45 primary gastric tumors, 17 biopsy samples of HPP- chronic gastritis, 23 H. pylori-negative (HPN) chronic gastritis, and 15 normal mucosa as the control. CDO1 expression levels were measured by immunohistochemical staining, and the methylation level of the promoter region was determined by quantitative methylation-specific PCR after bisulfite conversion. CDO1 gene promoter methylation levels were significantly higher in the gastric cancer (GC) group compared to the HPN-chronic gastritis and control groups (P = 0.000). There was no significant difference between the GC group and the HPP- chronic gastritis group. The CDO1 gene promoter methylation levels were higher in the HPP- chronic gastritis group than in the HPN-chronic gastritis group (P = 0.049). There was no significant difference between the study groups for the CDO1 immunopositivity score. The CDO1 gene promoter methylation levels are increased in GC and HPP-chronic gastritis patients. The CDO1 methylation, regardless of differences in protein expression, may be a promising non-invasive marker for early diagnosis of GC in HPP-chronic gastritis patients.