{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:41:22Z","timestamp":1776084082886,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08 DK124686"],"award-info":[{"award-number":["K08 DK124686"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Both M\u00e9n\u00e9trier'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\u2010alpha (TGF\u03b1), in the stomach. JPS is inherited in an autosomal dominant pattern and is caused by\n                    <jats:italic>BMPR1A<\/jats:italic>\n                    or\n                    <jats:italic>SMAD4<\/jats:italic>\n                    mutations. Although there are distinct clinico\u2010pathological 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\u2010associated oncogene homolog 1) and HHIP (Hedgehog\u2010interacting protein), is higher in MD than in JPS, particularly in foveolar cells by immunohistochemistry. We also demonstrated\u00a0that 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\u2010pathological 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. \u00a9 2025 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6488","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T06:11:11Z","timestamp":1762495871000},"page":"65-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of M\u00e9n\u00e9trier's disease"],"prefix":"10.1002","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9825-1016","authenticated-orcid":false,"given":"Miyoung","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tryston T","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred Kwame","family":"Ofosu","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tricia T","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew E","family":"Bechard","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J","family":"Coffey","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-5753","authenticated-orcid":false,"given":"Won Jae","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30491"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4132\/jptm.2015.09.15"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000320"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.220061"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2016.06.010"},{"key":"e_1_2_8_7_1","article-title":"A rare case of juvenile polyposis syndrome mimicking M\u00e9n\u00e9trier's disease","volume":"14","author":"Bernshteyn 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