Evidence map›Paper›PMID 42474615›Full record

ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2026

Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects.

Komei Kuge, Junko Mukohyama, Yoshimi Yasukawa, Yuko Ishibashi, Hiroki Masuda, Tomohiko Yasuda, Yasukazu Ohmoto, Hideyuki Takeshima, Akihisa Matsuda, Hiroshi Yoshida and 4 more

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Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Komei KugeDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Junko MukohyamaDivision of Frontier Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yoshimi YasukawaDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yuko IshibashiDepartment of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroki MasudaDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tomohiko YasudaDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yasukazu OhmotoDepartment of Pharmacokinetics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
Hideyuki TakeshimaDivision of Epigenomics, Institute for Advanced Life Sciences, Hoshi University, Tokyo, Japan.
Akihisa MatsudaDepartment of Gastroenterological Surgery, Nippon Medical School, Tokyo, Japan.
Hiroshi YoshidaDepartment of Gastroenterological Surgery, Nippon Medical School, Tokyo, Japan.
Yasuyuki SetoDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
James R GoldenringSection of Surgical Sciences, Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Toshikazu UshijimaDivision of Epigenomics, Institute for Advanced Life Sciences, Hoshi University, Tokyo, Japan.
Sachiyo NomuraDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sachiyo.nomura1012@gmail.com.ORCID http://orcid.org/0000-0003-4293-6205

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSerum trefoil factor 3 (TFF3) has emerged as a promising biomarker for gastric cancer; however, its biological origin remains unclear.

methodsGastric cancer was induced by Helicobacter pylori infection combined with N-methyl-N-nitrosourea (MNU), whereas a rat model was established using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone. Serum TFF levels were measured by ELISA. Organ-specific TFF3 expression, cytokine profiles, STAT3 activation, and epigenetic regulation were analyzed using RT-PCR, immunohistochemistry, multiplex assays, Western blotting, and ChIP-qPCR.

resultsSerum TFF1-3 levels were significantly elevated in gastric cancer-bearing mice, with TFF3 showing robust diagnostic performance. In rats, serum TFF3 levels remained unchanged after total gastrectomy. TFF3 expression was selectively upregulated in the liver, accompanied by STAT3 activation. Gastric IL-6 expression was increased, suggesting portal-mediated signaling to the liver. ChIP-qPCR demonstrated sustained enrichment of H3K27ac at the TFF3 locus following IL-6 stimulation.

conclusionsIncreased serum TFF3 in gastric cancer originates from the liver and is associated with IL-6-STAT3 signaling. Persistent elevation after gastrectomy may be explained by epigenetic activation, supporting the biological basis of TFF3 as a surrogate marker.

Indexed as

Biomarkers, TumorLiverStomach NeoplasmsTrefoil Factor-3AnimalsFemaleHelicobacter InfectionsHumansMaleMiceRatsSTAT3 Transcription FactorBiomarkers, TumorSTAT3 Transcription FactorTFF3 protein, humanTff3 protein, mouseTFF3 protein, ratTrefoil Factor-3Gastric cancerInterleukin-6STAT3Surrogate markersTrefoil factor 3

Identifiers

PMID42474615
PMCPMC13524970

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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.