Gut Liver.  2023 Sep;17(5):741-752. 10.5009/gnl220301.

Helicobacter pylori Eradication Can Reverse Rho GTPase Expression in Gastric Carcinogenesis

• Kim JL
• Kim SG
• Natsagdorj E
• Chung H
• Cho SJ

• KMID: 2546016
• DOI: http://doi.org/10.5009/gnl220301

Abstract

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 expression 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 reaction and the quantitative MethyLight assay, respectively. Changes in expression and methylation 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 betweenH. pylori-eradicated and -persistent GCs at the index endoscopic resection, those of H. pylori-persistent GCs increased and H. pylorieradicated 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.

Keyword

Helicobacter pylori; Rho GTPase; DNA methylation; Epigenetics; Stomach neoplasms