Helicobacter pylori Eradication Can Reverse Rho GTPase Expression in Gastric Carcinogenesis

Background/Aims: Altered DNA methylation is a key mechanism of epigenetic modification in gastric cancer (GC). This study aimed to evaluate the changes in epigenetic and genetic expres-sion of multiple Rho GTPases in Helicobacter pylori-related gastric carcinogenesis by comparing H. pylori-positive GCs and negative controls. Methods: The messenger RNA expression and methylation of Rho GTPases (RhoA, Rac1, DOCK180, ELMO1, and CDC42) were evaluated in H. pylori-negative (control) human gastric tissues and H. pylori-positive GCs by using real-time reverse transcription-polymerase chain re-action and the quantitative MethyLight assay, respectively. Changes in expression and methyla-tion levels of the genes were also compared between H. pylori-eradicated and-persistent GCs at 1-year follow-up. Results: In GCs, the methylation and expression levels of DOCK180 and ELMO1 were higher than in controls, while RhoA and Rac1 had lower levels than controls. CDC42 had the same expression pattern as DOCK180 and ELMO1 without DNA methylation. Although methylation levels of DOCK180 and ELMO1 had no difference between H. pylori-eradicated and-persistent GCs at the index endoscopic resection, those of H. pylori-persistent GCs increased and H. pylori- eradicated GCs decreased for 1 year. The expression levels of DOCK180, ELMO1, and CDC42 in H. pylori-persistent GCs were higher than those in H. pylori-eradicated GCs over 1 year, unlike those of RhoA and Rac1. The methylation levels at index and the degrees of change over time of RhoA and Rac1 had no difference between H. pylori-persistent and-eradicated GCs. Conclusions: Epigenetic alterations of DOCK180 and ELMO1 are involved in H. pylori-related gastric carcinogenesis. This epigenetic field could be improved by H. pylori eradication. (Gut Liver, Published online January 31, 2023)

Automated summary

This study evaluated the epigenetic and genetic expression changes of multiple Rho GTPases in Helicobacter pylori-related gastric carcinogenesis. It found that DOCK180 and ELMO1 had higher DNA methylation and expression levels in gastric cancer, while RhoA and Rac1 had lower levels. CDC42 had the same expression pattern as DOCK180 and ELMO1 without DNA methylation. The study also showed that H. pylori eradication could improve the epigenetic field of gastric carcinogenesis.