{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:41:41Z","timestamp":1785436901324,"version":"3.56.0"},"reference-count":96,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372344"],"award-info":[{"award-number":["82372344"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82372344"],"award-info":[{"award-number":["82372344"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Department of Science and Technology of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515011850"],"award-info":[{"award-number":["2024A1515011850"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024A1515011850"],"award-info":[{"award-number":["2024A1515011850"]}],"id":[{"id":"https:\/\/ror.org\/00tjzgn92","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is a highly aggressive malignancy that is difficult to diagnose early and carries a poor prognosis. Conventional serological diagnostics are limited by inadequate sensitivity and the risks of invasive procedures, resulting in most patients being diagnosed at an advanced stage. In recent years, liquid biopsy has emerged as a novel approach for non-invasive and dynamic molecular tumor monitoring by detecting biomarkers such as circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and clusterin (CLU). Furthermore, artificial intelligence (AI) has demonstrated strong potential in aiding diagnosis through medical image analysis, pathological pattern recognition, and multi-omics data integration, significantly improving the precision of early detection, risk stratification, and treatment response monitoring in CCA. This review systematically summarizes recent advances in liquid biopsy and AI for CCA diagnosis, discusses their clinical potential and current challenges, and offers perspectives on how their integration can propel the field toward earlier and more precise management of the disease.<\/jats:p>","DOI":"10.3390\/ijms27093779","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"3779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in In Vitro Diagnostics for Cholangiocarcinoma: From Biomarker Discovery to Artificial Intelligence"],"prefix":"10.3390","volume":"27","author":[{"given":"Chengrui","family":"Mo","sequence":"first","affiliation":[{"name":"Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2985-3766","authenticated-orcid":false,"given":"Tiancai","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrgastro.2011.20","article-title":"Cholangiocarcinoma\u2014Controversies and challenges","volume":"8","author":"Patel","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/S0140-6736(13)61903-0","article-title":"Cholangiocarcinoma","volume":"383","author":"Razumilava","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41575-025-01153-w","article-title":"Cholangiocarcinoma 2026: Status quo, unmet needs and priorities","volume":"23","author":"Banales","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/liv.14095","article-title":"Cholangiocarcinoma: Epidemiology and risk factors","volume":"39","author":"Khan","year":"2019","journal-title":"Liver Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.2147\/IJGM.S526759","article-title":"FGFR2-Rearrangement in Intrahepatic and Extrahepatic Cholangiocarcinoma and Prognostic Analysis","volume":"18","author":"Guo","year":"2025","journal-title":"Int. J. Gen. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/13543784.2021.1880565","article-title":"Key challenges for drugs in clinical development for cholangiocarcinoma","volume":"30","author":"Keenan","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1038\/ncomms6696","article-title":"Mutational landscape of intrahepatic cholangiocarcinoma","volume":"5","author":"Zou","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1158\/1078-0432.CCR-18-0078","article-title":"Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention","volume":"24","author":"Lowery","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jhep.2020.03.008","article-title":"Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma","volume":"73","author":"Montal","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10396-024-01491-3","article-title":"Advanced ultrasound diagnosis of extrahepatic bile duct lesions","volume":"52","author":"Okaniwa","year":"2025","journal-title":"J. Med. Ultrason."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s00261-024-04267-y","article-title":"Cholangiocarcinoma imaging: From diagnosis to response assessment","volume":"49","author":"Cao","year":"2024","journal-title":"Abdom. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.soc.2014.09.002","article-title":"Imaging approach to hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer","volume":"24","author":"Fowler","year":"2015","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bpg.2015.02.004","article-title":"Radiological diagnosis in cholangiocarcinoma: Application of computed tomography, magnetic resonance imaging, and positron emission tomography","volume":"29","author":"Ringe","year":"2015","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"405","DOI":"10.14309\/ajg.0000000000002190","article-title":"ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures","volume":"118","author":"Elmunzer","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1055\/a-2481-7048","article-title":"Diagnostic work-up of bile duct strictures: European Society of Gastrointestinal Endoscopy (ESGE) Guideline","volume":"57","author":"Facciorusso","year":"2025","journal-title":"Endoscopy"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3390\/curroncol30010030","article-title":"Pathology of Cholangiocarcinomas","volume":"30","author":"Guedj","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4868","DOI":"10.1016\/j.radcr.2022.09.061","article-title":"Bleeding after percutaneous transhepatic biliary drainage due to arterial injury: A case study in patient with stable hemodynamic","volume":"17","author":"Widyaningtiyas","year":"2022","journal-title":"Radiol. Case Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s00261-023-04064-z","article-title":"Diagnostic performance of magnetic resonance imaging and contrast-enhanced ultrasound in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma: A meta-analysis","volume":"49","author":"Wu","year":"2024","journal-title":"Abdom. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e78306","DOI":"10.2196\/78306","article-title":"Diagnostic Performance of Computed Tomography-Based Artificial Intelligence for Early Recurrence of Cholangiocarcinoma: Systematic Review and Meta-Analysis","volume":"27","author":"Chen","year":"2025","journal-title":"J. Med. Internet Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume":"145","author":"Ilyas","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"zrab127","DOI":"10.1093\/bjsopen\/zrab127","article-title":"Serum carcinoembryonic antigen and carbohydrate antigen 19-9 as preoperative diagnostic biomarkers of extrahepatic bile duct cancer","volume":"5","author":"Kim","year":"2021","journal-title":"BJS Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.cca.2018.02.008","article-title":"The diagnostic value of five serum tumor markers for patients with cholangiocarcinoma","volume":"480","author":"Qiu","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s43856-025-00885-9","article-title":"Expanding screening through the use of liquid biopsy for early cancer detection","volume":"5","author":"Perachino","year":"2025","journal-title":"Commun. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1126\/science.1228522","article-title":"Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition","volume":"339","author":"Yu","year":"2013","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4103\/aja.aja_1_18","article-title":"Utility of cell-free nucleic acid and circulating tumor cell analyses in prostate cancer","volume":"20","author":"Gourdin","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"748","DOI":"10.2174\/1381612829666230308102611","article-title":"Circulating Tumor Cells and Cell-free Nucleic Acids as Biomarkers in Colorectal Cancer","volume":"29","author":"Pourali","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/hep.27944","article-title":"Circulating tumor cells are associated with poor overall survival in patients with cholangiocarcinoma","volume":"63","author":"Yang","year":"2016","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-1-4939-2990-0_18","article-title":"Detection and Characterization of Circulating Tumor Cells by the CellSearch Approach","volume":"1347","author":"Coumans","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6881","DOI":"10.1021\/acs.analchem.3c02769","article-title":"Digital Circulating Tumor Cells Quantification","volume":"96","author":"Wang","year":"2024","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41571-023-00781-y","article-title":"Circulating tumour cells for early detection of clinically relevant cancer","volume":"20","author":"Lawrence","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1158\/1078-0432.CCR-17-1063","article-title":"Circulating Tumor Cells from Different Vascular Sites Exhibit Spatial Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical Significance in Hepatocellular Carcinoma","volume":"24","author":"Sun","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41568-019-0180-2","article-title":"Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells","volume":"19","author":"Keller","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Trifylli, E.L.N.M., Kriebardis, A.G., Koustas, E., Papadopoulos, N., Vasileiadi, S., Fortis, S.P., Tzounakas, V.L., Anastasiadi, A.T., Sarantis, P., and Papageorgiou, E.G. (2023). The Arising Role of Extracellular Vesicles in Cholangiocarcinoma: A Rundown of the Current Knowledge Regarding Diagnostic and Therapeutic Approaches. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115563"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/hep.27050","article-title":"Human bile contains microRNA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis","volume":"60","author":"Li","year":"2014","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1053\/j.gastro.2017.04.043","article-title":"Extracellular Vesicles in Bile as Markers of Malignant Biliary Stenoses","volume":"153","author":"Severino","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00535-025-02250-y","article-title":"Endoscopic liquid biopsy of bile: Superior diagnostic and prognostic performance of bile-derived exosomal miR-21-5p for biliary tract cancers","volume":"60","author":"Yoshida","year":"2025","journal-title":"J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/hep.29291","article-title":"Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma","volume":"66","author":"Arbelaiz","year":"2017","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jhep.2023.02.027","article-title":"Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma","volume":"79","author":"Lapitz","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"S\u0142omka, A., Kornek, M., and Cho, W.C. (2022). Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review. Cells, 11.","DOI":"10.3390\/cells11182913"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s12951-024-02459-8","article-title":"Circulating tumor cell-derived exosome-transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells","volume":"22","author":"Zhou","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"217596","DOI":"10.1016\/j.canlet.2025.217596","article-title":"Tumor-derived exosomal LINC01812 induces M2 macrophage polarization to promote perineural invasion in cholangiocarcinoma","volume":"617","author":"Wang","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/HEP.0000000000000437","article-title":"Bile exosomal miR-182\/183-5p increases cholangiocarcinoma stemness and progression by targeting HPGD and increasing PGE2 generation","volume":"79","author":"Shu","year":"2024","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/cr.2015.82","article-title":"Circular RNA is enriched and stable in exosomes: A promising biomarker for cancer diagnosis","volume":"25","author":"Li","year":"2015","journal-title":"Cell Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41392-024-01814-3","article-title":"Cholangiocarcinoma combined with biliary obstruction: An exosomal circRNA signature for diagnosis and early recurrence monitoring","volume":"9","author":"Wen","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.21037\/atm.2019.01.12","article-title":"Extracellular vesicles in hepatocellular cancer and cholangiocarcinoma","volume":"7","author":"Xie","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e20230031","DOI":"10.1002\/SMMD.20230031","article-title":"Emerging ctDNA detection strategies in clinical cancer theranostics","volume":"2","author":"Yi","year":"2023","journal-title":"Smart Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2400443","DOI":"10.1200\/PO-24-00443","article-title":"Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection","volume":"9","author":"Yu","year":"2025","journal-title":"JCO Precis. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00535-024-02175-y","article-title":"FGFR2 fusions assessed by NGS, FISH, and immunohistochemistry in intrahepatic cholangiocarcinoma","volume":"60","author":"Cao","year":"2025","journal-title":"J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kim, K.H.E., Yi, H.S., Lee, H., Bae, G.E., and Yeo, M.K. (2023). Targeting the Sequences of Circulating Tumor DNA of Cholangiocarcinomas and Its Applications and Limitations in Clinical Practice. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087512"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/14737159.2025.2518145","article-title":"Best practices in sample management and molecular profiling of cholangiocarcinoma: A practical guide","volume":"25","author":"Castet","year":"2025","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2100197","DOI":"10.1200\/PO.21.00197","article-title":"Monitoring of Dynamic Changes and Clonal Evolution in Circulating Tumor DNA From Patients With IDH-Mutated Cholangiocarcinoma Treated with Isocitrate Dehydrogenase Inhibitors","volume":"6","author":"Lapin","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"332","DOI":"10.4251\/wjgo.v13.i5.332","article-title":"Liquid biopsy in cholangiocarcinoma: Current status and future perspectives","volume":"13","author":"Rompianesi","year":"2021","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gao, L., Lin, Y., Yue, P., Li, S., Zhang, Y., Mi, N., Bai, M., Fu, W., Xia, Z., and Jiang, N. (2023). Identification of a novel bile marker clusterin and a public online prediction platform based on deep learning for cholangiocarcinoma. BMC Med., 21, Erratum in BMC Med.\u00a02023, 21, 368; Erratum in BMC Med.\u00a02024, 22, 179.","DOI":"10.1186\/s12916-023-02990-9"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100843","DOI":"10.1016\/j.medj.2025.100843","article-title":"Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin","volume":"6","author":"Gao","year":"2025","journal-title":"Med"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Selvaggi, F., Lopetuso, L.R., Delli Pizzi, A., Melchiorre, E., Murgiano, M., Taraschi, A.L., Cotellese, R., Diana, M., Vivarelli, M., and Mocchegiani, F. (2025). Diagnosis of Cholangiocarcinoma: The New Biological and Technological Horizons. Diagnostics, 15.","DOI":"10.3390\/diagnostics15081011"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ajpath.2024.06.013","article-title":"The Search for Risk, Diagnostic, and Prognostic Biomarkers of Cholangiocarcinoma and Their Biological and Clinicopathologic Significance","volume":"195","author":"Macias","year":"2025","journal-title":"Am. J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"104170","DOI":"10.3748\/wjg.v31.i11.104170","article-title":"Cholangiocarcinoma: The era of liquid biopsy","volume":"31","author":"Kotsifa","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/clinchem\/hvad194","article-title":"Critical Factors in the Analytical Work Flow of Circulating Tumor DNA-Based Molecular Profiling","volume":"70","author":"Schuuring","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.jhep.2024.10.020","article-title":"Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer","volume":"82","author":"Hwang","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"105079","DOI":"10.1016\/j.esmoop.2025.105079","article-title":"Precision oncology in biliary tract cancer: The emerging role of liquid biopsy","volume":"10","author":"Bortolot","year":"2025","journal-title":"ESMO Open"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jhep.2024.10.043","article-title":"Circulating tumor DNA status and dynamics predict recurrence in patients with resected extrahepatic cholangiocarcinoma","volume":"82","author":"Yoo","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e2300382","DOI":"10.1200\/PO.23.00382","article-title":"Recommendations for the Equitable and Widespread Implementation of Liquid Biopsy for Cancer Care","volume":"8","author":"Febbo","year":"2024","journal-title":"JCO Precis. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.annonc.2023.06.011","article-title":"ESMO study on the availability and accessibility of biomolecular technologies in oncology in Europe","volume":"34","author":"Bayle","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature14539","article-title":"Deep learning","volume":"521","author":"LeCun","year":"2015","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41591-018-0316-z","article-title":"A guide to deep learning in healthcare","volume":"25","author":"Esteva","year":"2019","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/hep.22310","article-title":"Cholangiocarcinoma: Advances in pathogenesis, diagnosis, and treatment","volume":"48","author":"Blechacz","year":"2008","journal-title":"Hepatology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1038\/modpathol.2017.51","article-title":"Cytologic predictors of malignancy in bile duct brushings: A multi-reviewer analysis of 60 cases","volume":"30","author":"Avadhani","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"eabk3112","DOI":"10.1126\/science.abk3112","article-title":"From telomere to telomere: The transcriptional and epigenetic state of human repeat elements","volume":"376","author":"Hoyt","year":"2022","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eadj9283","DOI":"10.1126\/scitranslmed.adj9283","article-title":"Genome-wide repeat landscapes in cancer and cell-free DNA","volume":"16","author":"Annapragada","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8290","DOI":"10.1038\/s41467-023-43749-3","article-title":"Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma","volume":"14","author":"Calderaro","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","article-title":"Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 study","volume":"21","author":"Sahai","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1056\/NEJMoa2206834","article-title":"Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma","volume":"388","author":"Goyal","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41467-023-36399-y","article-title":"Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers","volume":"14","author":"Harding","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jhep.2025.01.011","article-title":"Contrast-enhanced ultrasound-based AI model for multi-classification of focal liver lesions","volume":"83","author":"Ding","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e250078","DOI":"10.1148\/rycan.250078","article-title":"Improving Detection of Intrahepatic Cholangiocarcinoma with a Contrast-enhanced US-based Deep Learning Model","volume":"7","author":"Ding","year":"2025","journal-title":"Radiol. Imaging Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/HEP.0000000000001283","article-title":"Spatial single-cell proteomics landscape decodes the tumor microenvironmental ecosystem of intrahepatic cholangiocarcinoma","volume":"83","author":"Hong","year":"2026","journal-title":"Hepatology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3350\/cmh.2024.0895","article-title":"Radiogenomics of intrahepatic cholangiocarcinoma predicts immunochemotherapy response and identifies therapeutic target","volume":"31","author":"Ji","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41571-021-00560-7","article-title":"Predicting cancer outcomes with radiomics and artificial intelligence in radiology","volume":"19","author":"Bera","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","article-title":"Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"eabn3774","DOI":"10.1126\/sciadv.abn3774","article-title":"Therapeutic strategies targeting uPAR potentiate anti-PD-1 efficacy in diffuse-type gastric cancer","volume":"8","author":"Qin","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Singh, Y., Andersen, J.B., Hathaway, Q.A., Vera-Garcia, D.V., Keishing, V., Venkatesh, S.K., Salehi, S., Povero, D., Wallace, M.B., and Gores, G.J. (2025). Leveraging Multimodal Foundation Models in Biliary Tract Cancer Research. Tomography, 11.","DOI":"10.3390\/tomography11090096"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41586-024-07894-z","article-title":"A pathology foundation model for cancer diagnosis and prognosis prediction","volume":"634","author":"Wang","year":"2024","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Abulibdeh, R., Celi, L.A., and Sejdi\u0107, E. (2025). The illusion of safety: A report to the FDA on AI healthcare product approvals. PLoS Digit. Health, 4.","DOI":"10.1371\/journal.pdig.0000866"},{"key":"ref_86","first-page":"40","article-title":"Evaluating the Impact of the EU AI Act on Medical Device Regulation","volume":"323","author":"Kalodanis","year":"2025","journal-title":"Stud. Health Technol. Inform."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e75527","DOI":"10.2196\/75527","article-title":"Balancing Innovation and Control: The European Union AI Act in an Era of Global Uncertainty","volume":"4","author":"Bignami","year":"2025","journal-title":"JMIR AI"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Godoy Junior, C.A., Boverhof, B.J., Rutten-van M\u00f6lken, M.P.M.H., Bijleveld, L., Westhuis, B., Groot, C.U.D., and Redekop, K. (Value Health, 2026). Technological Maturity and Cost-Effectiveness of Medical Artificial Intelligence: A Systematic Review of Health Economic Evaluations, Value Health, in press.","DOI":"10.1016\/j.jval.2026.01.014"},{"key":"ref_89","first-page":"386","article-title":"Statistical Rigor and Reproducibility in the AI Era","volume":"42","author":"Korkmaz","year":"2025","journal-title":"Balk. Med. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105970","DOI":"10.1016\/j.ijmedinf.2025.105970","article-title":"Show and tell: A critical review on robustness and uncertainty for a more responsible medical AI","volume":"202","author":"Marconi","year":"2025","journal-title":"Int. J. Med. Inform."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"125","DOI":"10.5306\/wjco.v13.i2.125","article-title":"Artificial intelligence and cholangiocarcinoma: Updates and prospects","volume":"13","author":"Haghbin","year":"2022","journal-title":"World J. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"AIp2500705","DOI":"10.1056\/AIp2500705","article-title":"Evaluating Translational AI: A Two-Way Moving Target Problem","volume":"2","author":"Leuchter","year":"2025","journal-title":"NEJM AI"},{"key":"ref_93","first-page":"677","article-title":"Beyond black boxes: Using explainable causal artificial intelligence to separate signal from noise in pharmacovigilance","volume":"48","author":"Ribeiro","year":"2026","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"AIpc2500871","DOI":"10.1056\/AIpc2500871","article-title":"Catalyzing Health AI by Fixing Payment Systems","volume":"2","author":"Razavian","year":"2025","journal-title":"NEJM AI"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sidabraite, A., Mosert, P.L., Ahmed, U., Jones, S.K., and Gulla, A. (2025). Advancing Cholangiocarcinoma Diagnosis: The Role of Liquid Biopsy and CRISPR\/Cas Systems in Biomarker Detection. Cancers, 17.","DOI":"10.3390\/cancers17132155"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Theocharopoulos, C., Theocharopoulos, A., Papadakos, S.P., Machairas, N., and Pawlik, T.M. (2025). Deep Learning to Enhance Diagnosis and Management of Intrahepatic Cholangiocarcinoma. Cancers, 17.","DOI":"10.3390\/cancers17101604"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3779\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:14:44Z","timestamp":1778213684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":96,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27093779"],"URL":"https:\/\/doi.org\/10.3390\/ijms27093779","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}