A comparative study of CDO1 promoter methylation in gastric cancer and H. pylori-associated chronic gastritis: Implications for diagnostic performance.

Authors

Selin Kankaya, Metehan Karatas, Engin Hatipoglu, Nuray Kepil, Zulal Kaptan, Zeynep Caliskan, Matem Tuncdemir, Yildiz Dincer

Published in

PloS one. Volume 21. Issue 8. Pages e0335832. Epub Aug 12, 2026.

Abstract

Silencing of the Cysteine dioxygenase-1 (CDO1) tumor suppressor gene by aberrant DNA methylation contributes to gastric carcinogenesis. Despite evidence that Helicobacter pylori (H. pylori) infection induces aberrant DNA methylation in the gastric mucosa, CDO1 promoter methylation has not been well characterized in H. Pylori positive (HPP) patients with chronic gastritis. This study aimed to investigate the CDO1 promoter methylation levels in patients with chronic gastritis with and without H. pylori infection, in comparison with gastric tumors. The quantitative analysis of CDO1 promoter methylation and CDO1 immunopositivity was performed in 45 primary gastric tumors, 17 biopsy samples of HPP chronic gastritis, 23 H. Pylori negative (HPN) chronic gastritis, and 15 normal gastric mucosa samples (control group). CDO1 expression was evaluated by immunohistochemistry, and promoter methylation levels were determined using quantitative methylation-specific PCR following bisulfite conversion. CDO1 promoter methylation levels were significantly higher in the gastric cancer (GC) group compared to the HPN chronic gastritis and control groups (p < 0.001). No significant difference was observed between the GC and HPP chronic gastritis groups. However, CDO1 promoter methylation levels were significantly higher in the HPP group compared to the HPN group (p = 0.049). No significant differences in CDO1 immunopositivity were observed among the study groups. ROC analysis demonstrated good discriminative ability of CDO1 methylation between GC and non-cancer cases (AUC = 0.83), whereas its performance was more limited in distinguishing GC from HPP chronic gastritis (AUC = 0.67). CDO1 promoter methylation is increased in GC and HPP chronic gastritis, suggesting that H. pylori-associated chronic inflammation may be associated with early epigenetic alterations. Although no direct correlation with protein expression was observed, our findings suggest that while CDO1 methylation may be informative for identifying cancer-related epigenetic changes, it may be insufficient as a standalone biomarker in high-risk inflammatory conditions. Further studies are needed to clarify its clinical utility, particularly in high-risk populations.

PMID:
42585240
Bibliographic data and abstract were imported from PubMed on 13 Aug 2026.

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