{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:21:28Z","timestamp":1787656888473,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272952"],"award-info":[{"award-number":["82272952"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M721579"],"award-info":[{"award-number":["2022M721579"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>While precision oncology increasingly adopts tissue\u2010agnostic paradigms, current strategies remain heavily reliant on molecular alterations, with limited relevance to early\u2010stage cancers and precancerous lesion management. Here we present an unsupervised and interpretable artificial intelligence framework that defines tissue\u2010agnostic cellular morphometric biomarkers (CMBs) capturing conserved tumor microenvironment (TME) architectures associated with cancer progression across gastrointestinal (GI) organs. Discovered from colorectal cancer whole\u2010slide images and validated in gastric and esophageal malignancies within a multi\u2010center cohort of 2,602 patients, a 13\u2010CMB signature demonstrates robust cross\u2010GI tissue transferability and prognostic impact. Importantly, beyond prognostic value in pan\u2010GI cancers, the 13\u2010CMB signature enables risk stratification of precancerous lesions and early\u2010stage cancers, addressing a key unmet need in clinical decision\u2010making where molecular profiling is often impractical or insufficient. The CMB\u2010based risk scores support risk\u2010adapted management, including individualized surveillance intervals and tailored intervention strategies. Integrative analyses using bulk and single\u2010cell RNA sequencing and immunohistochemistry profiling show that CMBs correspond to biologically interpretable morphological states of the TME, including immune\u2010excluded and stromal\u2010dominant architectures. Together, this study establishes a biologically transparent, tissue\u2010agnostic CMB framework that links conserved TME organization to clinically actionable risk assessment, providing a scalable approach for early cancer management and precision oncology.<\/jats:p>","DOI":"10.1002\/advs.77353","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:46:13Z","timestamp":1787654773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tissue\u2010Agnostic Cellular Morphometric Biomarkers for Risk\u2010Adapted Management Across Gastrointestinal Precancerous Lesions and Cancers"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8939-5413","authenticated-orcid":false,"given":"Pin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Oncology Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Liver Cancer Institute Zhongshan Hospital Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education) Fudan University  Shanghai China"},{"name":"National Clinical Research Center for Interventional Medicine  Shanghai China"},{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu China"},{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengfei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April W.","family":"Mao","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"},{"name":"Department of Mathematics University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-0027","authenticated-orcid":false,"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery and Liver Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6056-1219","authenticated-orcid":false,"given":"Jamie L.","family":"Inman","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Celniker","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"},{"name":"Berkeley Biomedical Data Science Center Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-1063","authenticated-orcid":false,"given":"Antoine M.","family":"Snijders","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"},{"name":"Berkeley Biomedical Data Science Center Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-1635","authenticated-orcid":false,"given":"David W.","family":"Threadgill","sequence":"additional","affiliation":[{"name":"Department of Nutrition Texas A&amp;M University  College Station Texas USA"},{"name":"Department of Molecular and Cellular Medicine and Department of Biochemistry &amp; Biophysics Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Balmain","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center University of California San Francisco  San Francisco USA"},{"name":"Department of Biochemistry and Biophysics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Hang","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Chang","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"},{"name":"Berkeley Biomedical Data Science Center Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-5930","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9320-6021","authenticated-orcid":false,"given":"Jian\u2010Hua","family":"Mao","sequence":"additional","affiliation":[{"name":"Biological Systems and Engineering Division Lawrence Berkeley National Laboratory  Berkeley California USA"},{"name":"Berkeley Biomedical Data Science Center Lawrence Berkeley National Laboratory  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200690"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.1840"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02005"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2728"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11404"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.034"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201016\u20102211"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_173855"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573\u2010022\u201000187\u2010y"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.9128"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp2210638"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010019\u20100252\u2010y"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.819565"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac154"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ced\/llad264"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010031\u201006573\u2010610.1007\/978\u20103\u2010031\u201006573\u20106_16"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.08.035"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.708.65.3"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad7297"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(23)00366\u20107"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010024\u201000932\u20109"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010021\u201000492\u20102"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010021\u201000473\u20105"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010019\u20100241\u20101"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.07.055"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v13.i7.616"},{"key":"e_1_2_12_30_1","first-page":"3","article-title":"Stacked Predictive Sparse Decomposition for Classification of Histology Sections","volume":"13","author":"Chang H.","year":"2014","journal-title":"International Journal of Computer Vision"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.3.424"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.07.006"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.007"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(23)00004\u20103"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2018.07.037"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2019.08.018"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77353","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:46:14Z","timestamp":1787654774000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":35,"alternative-id":["10.1002\/advs.77353"],"URL":"https:\/\/doi.org\/10.1002\/advs.77353","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"assertion":[{"value":"2025-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77353"}}