Evidence map›Paper›PMID 40668443›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2025

Concurrent hypermethylation of CpG islands and hypomethylation of CpG-poor regions are associated with gastric cancer risk after Helicobacter pylori eradication.

Gota Sudo, Eiichiro Yamamoto, Takeshi Niinuma, Mitsunobu Saito, Hiroshi Kitajima, Kazuya Ishiguro, Akira Yorozu, Mutsumi Toyota, Hironori Aoki, Kei Mitsuhashi and 7 more

Abstract read
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In one paragraph

Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Advances inOncology letters · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Military Medical Research · 2026
    Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Gota SudoDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Eiichiro YamamotoDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Takeshi NiinumaDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Mitsunobu SaitoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hiroshi KitajimaDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Kazuya IshiguroDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Akira YorozuDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Mutsumi ToyotaDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Hironori AokiDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan.
Kei MitsuhashiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Shinji YoshiiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hiro-O YamanoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Masashi IdogawaDivision of Medical Genome Sciences, Department of Genomic and Preventive Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Reo MaruyamaDivision of Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Tamotsu SugaiDepartment of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Shiwa-gun, Japan.
Hiroshi NakaseDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hiromu SuzukiDivision of Molecular Biology, Department of Biochemistry, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo, 060-8556, Japan. hsuzuki@sapmed.ac.jp.ORCID 0000-0001-9635-3238

Funding

Japan Society for the Promotion of Science 21K07985Japan Society for the Promotion of Science 22K07964Japan Society for the Promotion of Science 22K16001Japan Society for the Promotion of Science 23K07420Japan Society for the Promotion of Science 23K24186Japan Society for the Promotion of Science 24K11157
6 · The paper itself

Abstract

BACKGROUND AND

aimAberrant DNA methylation persists in the gastric mucosa after Helicobacter pylori (H. pylori) eradication and may contribute to the development of post-eradication gastric cancer (PEGC). We aimed to comprehensively investigate both DNA hypermethylation and hypomethylation and their relevance to cancer risk.

methodsGenome-wide DNA methylation profiling was performed using Infinium MethylationEPIC BeadChips with tumor tissue and non-cancerous mucosa from PEGC patients. Public datasets, including The Cancer Genome Atlas (TCGA)-STAD and H. pylori-negative controls, were integrated to identify recurrently hyper- and hypomethylated loci. Representative gene methylation levels were validated using bisulfite pyrosequencing. Correlation analyses were conducted to link DNA methylation with gene expression.

resultsNon-cancerous mucosa from PEGC patients exhibited substantial CpG island (CGI) hypermethylation. In parallel, we detected 4081 CpG sites recurrently hypomethylated in GC, many of which were also hypomethylated in non-cancerous mucosa from PEGC patients. The majority of hypomethylated sites were located outside of CGIs, often near oncogenes such as CDH17, HNF4A and CD44, and showed inverse correlations with gene expression. CGI hypermethylation and CpG hypomethylation were positively correlated across samples.

conclusionsCGI hypermethylation and non-CGI hypomethylation are tightly linked and may co-emerge during the early stages of gastric carcinogenesis. Their concurrent presence in non-cancerous mucosa from PEGC patients suggests a coordinated epigenetic landscape contributing to residual cancer risk after H. pylori eradication.

Indexed as

CpG IslandsEpigenesis, GeneticHelicobacter InfectionsStomach NeoplasmsAgedAged, 80 and overBiopsyCarcinogenesisDinucleoside PhosphatesDNA MethylationFemaleGastric MucosaGastroscopyGene Expression Regulation, NeoplasticHelicobacter pyloriHumansCpG dinucleotideDinucleoside PhosphatesHelicobacter pyloriHypermethylationHypomethylationPost-eradication gastric cancer

Identifiers

PMID40668443

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.