{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:58:47Z","timestamp":1785517127916,"version":"3.56.0"},"reference-count":28,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Digestion"],"abstract":"<jats:p>Introduction: High-risk chronic atrophic gastritis (CAG; OLGA\/OLGIM \u2162-\u2163) carries significant gastric cancer (GC) risk yet lacks reliable gastric stem cell (GSC)-based biomarkers. We evaluated GSC markers LGR5 (proliferative) and TFF2 (protective) for risk stratification. Methods: TCGA\/GEO bioinformatics analysis preceded immunohistochemical validation in 60 clinical samples. Protein co-expression (Wnt\/\u03b2-catenin, Ki67, Bax) was assessed. Diagnostic\/prognostic power was tested via ROC and Kaplan-Meier analyses. Functional networks were deciphered through GO\/KEGG enrichment. Results: High-risk CAG and GC tissues showed LGR5 upregulation and TFF2 downregulation (p &lt; 0.001). IHC confirmed these patterns, with concurrent Wnt activation (\u03b2-catenin\u2191, cyclin D1\u2191) and proliferation-apoptosis imbalance (Ki67\u2191, Bax\u2193). TFF2 outperformed LGR5 in diagnosing high-risk CAG (AUC: 0.842 vs. 0.681). Poor GC prognosis correlated with high LGR5\/low TFF2 (p &lt; 0.05). Co-expression networks linked LGR5 to metabolic genes (CPS1, ADH6) and TFF2 to mucosal defense (GKN1, PGC). Conclusion: The coordinated assessment of LGR5 and TFF2 offers a promising approach to identifying high-risk CAG. This biomarker pair captures a homeostatic imbalance in GSCs linked to Wnt\/\u03b2-catenin signaling, establishing a novel molecular framework for early detection and future targeted strategies.<\/jats:p>","DOI":"10.1159\/000549887","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T17:00:35Z","timestamp":1769274035000},"page":"1-19","source":"Crossref","is-referenced-by-count":0,"title":["Identification of LGR5 and TFF2 as Biomarkers in High-Risk Chronic Atrophic Gastritis: From Multi-Omics Mining to Clinical Validation"],"prefix":"10.1159","author":[{"given":"Qingqing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijing","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-022-00677-6"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000003733"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-332594"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.01.037"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.02.009"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S355981"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.12.001"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2012.00618.x"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1002\/path.4096"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.08.003"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00667"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1177\/15330338241242635"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-024-15783-y"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01741"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2739"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.08.043"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122648"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0190"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.019"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/nature22359"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.retram.2019.08.003"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-007-0135-4"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-008-0028-7"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2008.05.001"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301717"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.044"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3385"}],"updated-by":[{"DOI":"10.1159\/000553198","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000}}],"container-title":["Digestion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000549887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:01:09Z","timestamp":1772211669000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000549887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,24]]},"references-count":28,"URL":"https:\/\/doi.org\/10.1159\/000549887","archive":["Portico"],"relation":{},"ISSN":["0012-2823","1421-9867"],"issn-type":[{"value":"0012-2823","type":"print"},{"value":"1421-9867","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,24]]}}}