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, 9 (1), 12559

DNA Methylation Silencing of microRNA Gene Methylator in the Precancerous Background Mucosa With and Without Gastric Cancer: Analysis of the Effects of H. Pylori Eradication and Long-Term Aspirin Use

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DNA Methylation Silencing of microRNA Gene Methylator in the Precancerous Background Mucosa With and Without Gastric Cancer: Analysis of the Effects of H. Pylori Eradication and Long-Term Aspirin Use

Jiro Watari et al. Sci Rep.

Abstract

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as miR-34c, miR-124a-3, miR-129-2, and miR-137, in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in non-IM, but not in IM. miR-129-2 methylation in non-IM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of H. pylori infection. miR-129-2 methylation in non-IM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Incidences of miRNA methylation in non-IM in three different parts of the stomach in patients not taking LDA/NSAIDs. (A) In H. pylori-infected patients, the miR-34-c methylation rate in the antrum (p = 0.03) and corpus (p = 0.01) was significantly higher in the Hp+/GC group than it was in the Hp+/AG group. Also, miR-129-2 methylation in non-IM in the corpus was more frequently identified in the Hp+/GC group than in the Hp+/AG group (p = 0.01). (B) In H. pylori-eradicated patients, the miR-129-2 methylation rate in the angulus in the Hp−/GC group was significantly higher than that in the Hp−/AG group (p = 0.01). LDA, low-dose aspirin; NSAID, nonsteroidal anti-inflammatory drug.
Figure 2
Figure 2
Incidences of miRNA methylation in non-IM in the three parts of the stomach in patients regularly taking LDA/NSAIDs. (A) In H. pylori-infected patients, there were no significant differences in the incidences of miRNA methylation in each portion of the stomach. (B) In H. pylori-eradicated patients, the miR-129-2 methylation rate in the antrum was significantly higher in the Hp−/GC group than it was in the Hp−/AG group (p = 0.04). LDA, low-dose aspirin; NSAID, nonsteroidal anti-inflammatory drug.

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