{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:05:29Z","timestamp":1784610329107,"version":"3.55.0"},"reference-count":142,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the program for science and technology development in Henan Province","award":["252102310322"],"award-info":[{"award-number":["252102310322"]}]},{"name":"the program for science and technology development in Henan Province","award":["252102311118"],"award-info":[{"award-number":["252102311118"]}]},{"name":"the program for science and technology development in Henan Province","award":["262102310117"],"award-info":[{"award-number":["262102310117"]}]},{"name":"the program for science and technology development in Henan Province","award":["262102310208"],"award-info":[{"award-number":["262102310208"]}]},{"name":"the program for science and technology development in Henan Province","award":["252102310098"],"award-info":[{"award-number":["252102310098"]}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan","doi-asserted-by":"crossref","award":["232300420262"],"award-info":[{"award-number":["232300420262"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelial cells of the biliary tract. It is characterized by high heterogeneity, frequent late diagnosis, high rates of metastasis, and overall poor prognosis. Unfortunately, the development of sensitive biomarkers and effective therapeutic approaches remains challenging and an unmet need. In recent years, advances in molecular biological techniques have significantly enhanced our understanding of the molecular mechanisms underlying CCA pathogenesis. This review summarized the biomarkers identified in CCA, highlighted the critical genes and signal transduction pathways closely associated with tumor cell proliferation and migration, inflammation regulation, angiogenesis, and tumor microenvironment, and discussed the complex regulatory roles of epigenetic alterations in CCA initiation and progression. These recent insights not only deepen our understanding of the molecular complexity of CCA but also lay a solid foundation for the development of precision medicine and individualized therapeutic strategies for patients with this aggressive malignancy.<\/jats:p>","DOI":"10.3390\/ijms27146362","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"6362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7397-8881","authenticated-orcid":false,"given":"Yange","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"},{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Yang","sequence":"additional","affiliation":[{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0047-6825","authenticated-orcid":false,"given":"Meijing","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Medical School, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meina","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"},{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"},{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6645-5786","authenticated-orcid":false,"given":"Xiangqian","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"},{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.31557\/APJCP.2023.24.3.741","article-title":"Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review","volume":"24","author":"Idris","year":"2023","journal-title":"Asian Pac. 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