{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:34:11Z","timestamp":1790620451351,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intestinal\u2010type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low\u2010grade intraepithelial neoplasia (LGIN) and high\u2010grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity\u2010changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five\u2010gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease\u2010free survival of GC patients (log\u2010rank test: <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and the robustness was verified in an independent cohort (<jats:italic>n<\/jats:italic>\u2009&gt;\u2009300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer\u2010like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. \u00a9 2020 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5434","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T09:11:07Z","timestamp":1585041067000},"page":"135-146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal\u2010type gastric cancer tumorigenesis"],"prefix":"10.1002","volume":"251","author":[{"given":"Yajing","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis National Cancer 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebing","family":"Di","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis National Cancer Center\/National Clinical Research Center for Cancer\/Cancer 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