Long-term effects of H. pylori eradication on epigenetic alterations related to gastric carcinogenesis

• Published in: Scientific reports Vol. 8; no. 1; pp. 14369 - 13
• Main Authors: Michigami, Yuki, Watari, Jiro, Ito, Chiyomi, Nakai, Keisuke, Yamasaki, Takahisa, Kondo, Takashi, Kono, Tomoaki, Tozawa, Katsuyuki, Tomita, Toshihiko, Oshima, Tadayuki, Fukui, Hirokazu, Morimoto, Takeshi, Das, Kiron M., Miwa, Hiroto
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-09-2018; Nature Publishing Group
• Subjects: 38/1; 38/39; 45/22; 45/77; 631/67/1504/1829; 692/4020/1503/1504/1829; 692/420/2489/2487/2486; 692/53/2423; Biopsy; Carcinogenesis; CpG islands; DNA methylation; Gastric cancer; Gastric mucosa; Gastritis; Helicobacter pylori; Humanities and Social Sciences; Intestine; Long-term effects; Methylation; Mucous membrane; multidisciplinary; Pathogens; Patients; Phenotypes; Science; Science (multidisciplinary); Gastric Cancer; Atrophic Gastritis; Pylori Eradication; Pylori Treatment; CpG Island Methylator Phenotype (CIMP)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-32717-3

The risk of gastric cancer (GC) remains in precancerous conditions, including atrophic mucosa and intestinal mucosa (IM), even after
H
.
pylori
treatment. To define the molecular changes following
H
.
pylori
eradication, molecular alterations in the gastric mucosa with and without GC were evaluated in a long-term follow-up study. A total of 232 biopsy specimens from 78 consecutive patients, including atrophic gastritis patients with follow-up ≥3 y after successful
H
.
pylori
eradication (AG group), patients who developed early GC after successful eradication (≥3 y) (GC group), and patients with
H
.
pylori
-positive atrophic gastritis (
Hp
group), were analyzed.
H
.
pylori
eradication was associated with significant reductions of methylation of several genes/loci in atrophic mucosa (non-IM), but not in IM. In contrast, the incidence of CpG island methylator phenotype (CIMP) in IM was significantly higher in the GC group than in the AG group.
miR-124a-3
methylation and
miR-34c
methylation were more frequently identified in IM, with very few in non-IM mucosa among the three groups.
H
.
pylori
eradication can reverse methylation only in non-IM mucosa. CIMP in IM may have potential as a surrogate maker of GC development, and methylation of
miR-124a-3
and
miR-34c
is a molecular event in IM that may not be associated with GC development.