Evidence map›Paper›PMID 41199529›Full record

ArticleThe Journal of pathology2026

Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.

Miyoung Shin, Tryston T Gabriel, Fred Kwame Ofosu, Jiali Zhang, Tricia T Wang, Matthew E Bechard, Robert J Coffey, Won Jae Huh

Abstract read
In one paragraph

Article in The Journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Miyoung ShinDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID https://orcid.org/0000-0001-9825-1016
Tryston T GabrielDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Fred Kwame OfosuDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Jiali ZhangDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Tricia T WangDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Matthew E BechardDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Robert J CoffeyDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Won Jae HuhDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID https://orcid.org/0000-0002-6695-5753

Funding

Integrated approach to study early and late events in colonic neoplasia: mouse to manR35CA197570 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Robert J. Coffey · 2017 to 2026
$9.4M
EGF Receptor and Notch Signaling in the Pathogenesis of Menetrier's DiseaseK08DK124686 · NIDDK · YALE UNIVERSITY · PI HUH, WON JAE · 2020 to 2024
$732k
NCI NIH HHS R35 CA197570NIDDK NIH HHS K08 DK124686
6 · The paper itself

Abstract

Both Ménétrier's disease (MD) and juvenile polyposis syndrome (JPS) are rare premalignant conditions that can lead to gastric cancer. MD is an acquired disease without known causative mutations that is characterized by increased expression of an EGF receptor (EGFR) ligand, transforming growth factor-alpha (TGFα), in the stomach. JPS is inherited in an autosomal dominant pattern and is caused by BMPR1A or SMAD4 mutations. Although there are distinct clinico-pathological features that differ between the two diseases, they also share similar features that often lead to misdiagnosis. To identify diagnostic markers for MD and to better understand the pathogenesis of the disease, we performed transcriptomic profiling of stomach tissues from normal (NL), MD, and JPS patients. Comparative analysis between MD and JPS revealed both common and differential gene signatures. Common gene signatures included estrogen receptor signaling, integrin signaling, mTOR signaling, and others, which may be responsible for histopathological similarities. Among differential gene signatures, we found that Hedgehog (Hh) signaling is upregulated in MD and confirmed that protein expression of Hh signaling downstream targets, GLI1 (glioma-associated oncogene homolog 1) and HHIP (Hedgehog-interacting protein), is higher in MD than in JPS, particularly in foveolar cells by immunohistochemistry. We also demonstrated that treatment with an Hh pathway inhibitor partially rescued the histopathological phenotypes in an MD mouse model. This study provides valuable insights into the potential mechanisms underlying the similar clinico-pathological features observed in MD and JPS. We also identified GLI1 and HHIP as diagnostic markers that can help to distinguish MD from JPS. Furthermore, Hh signaling was shown to play an important role in the pathogenesis of MD and may serve as a potential therapeutic target. © 2025 The Pathological Society of Great Britain and Ireland.

Indexed as

Gene Expression ProfilingHedgehog ProteinsSignal TransductionTranscriptomeAnimalsBiomarkersDisease Models, AnimalFemaleHumansMaleMiceZinc Finger Protein GLI1BiomarkersGLI1 protein, humanHedgehog ProteinsZinc Finger Protein GLI1EGFR signalingHedgehog signalingjuvenile polyposis syndromeMénétrier's diseasepreneoplasiastomach

Identifiers

PMID41199529
PMCPMC13045204

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Registered trials

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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.