{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:57:05Z","timestamp":1784901425750,"version":"3.55.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. It often lacks distinct symptoms in its early stages, and no specific biomarkers have yet been identified for its diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify key genes involved in GBC pathogenesis using public databases and bioinformatics analysis and validate these findings experimentally, providing a foundation for developing potential GBC biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analysis of GBC-related data from the Gene Expression Omnibus database revealed that G protein-coupled receptor 64 (GPR64) was differentially expressed in GBC. GPR64 expression in GBC-SD and NOZ cells was modulated using lentiviral transfection. Functional assays assessed cancer-related phenotypes, while apoptosis was measured using flow cytometry. Xenograft models in nude mice were established with cell lines overexpressing GPR64.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GPR64 expression was reduced in GBC. Its overexpression suppressed GBC cell invasion, migration, and proliferation, and induced apoptosis. <jats:italic>In vivo<\/jats:italic> findings were consistent with <jats:italic>in vitro<\/jats:italic> results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GPR64 plays a critical role in GBC pathogenesis and may serve as a promising biomarker for its diagnosis and treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1643366","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:34:53Z","timestamp":1756964093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification and verification of the key genes involved in gallbladder cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Jie","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengyi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2024.05.02","article-title":"Epidemiology of biliary tract cancer in China: A narrative review","volume":"36","author":"Zhou","year":"2024","journal-title":"Chin J Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2022.04.007","article-title":"Worldwide incidence and mortality of biliary tract cancer","volume":"1","author":"Baria","year":"2022","journal-title":"Gastro Hep Adv"},{"key":"B3","doi-asserted-by":"publisher","first-page":"107064","DOI":"10.1016\/j.ejso.2023.107064","article-title":"Epidemiology of cholangiocarcinoma","volume":"51","author":"Qurashi","year":"2025","journal-title":"Eur J Surg Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2024.04.003","article-title":"Cholangiocarcinoma","volume":"104","author":"Harrison","year":"2024","journal-title":"Surg Clin North Am"},{"key":"B5","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/s41392-020-00324-2","article-title":"Overview of current targeted therapy in gallbladder cancer","volume":"5","author":"Song","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.21037\/cco.2019.08.14","article-title":"Systemic therapy for gallbladder cancer","volume":"8","author":"Javle","year":"2019","journal-title":"Chin Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41572-022-00398-y","article-title":"Gallbladder cancer","volume":"8","author":"Roa","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"B8","doi-asserted-by":"publisher","first-page":"106234","DOI":"10.1016\/j.ijsu.2022.106234","article-title":"Current management of incidental gallbladder cancer: A review","volume":"98","author":"Feo","year":"2022","journal-title":"Int J Surg"},{"key":"B9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.21037\/cco.2019.06.06","article-title":"Gallbladder cancer: surgical management","volume":"8","author":"Krell","year":"2019","journal-title":"Chin Clin Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2018.12.008","article-title":"Gallbladder cancer: diagnosis, surgical management, and adjuvant therapies","volume":"99","author":"Hickman","year":"2019","journal-title":"Surg Clin North Am"},{"key":"B11","doi-asserted-by":"publisher","first-page":"re3","DOI":"10.1126\/scisignal.2003825","article-title":"Sticky signaling\u2013adhesion class G protein-coupled receptors take the stage","volume":"6","author":"Langenhan","year":"2013","journal-title":"Sci Signal"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009647","article-title":"International Union of Basic and Clinical Pharmacology. 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