{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:56:28Z","timestamp":1781286988934,"version":"3.54.1"},"reference-count":103,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W18XWH-21-1-0798"],"award-info":[{"award-number":["W18XWH-21-1-0798"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HT94252510974"],"award-info":[{"award-number":["HT94252510974"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50 CA 210964"],"award-info":[{"award-number":["P50 CA 210964"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-23-1037312-01-IBCD"],"award-info":[{"award-number":["RSG-23-1037312-01-IBCD"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastroenterol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Perihilar cholangiocarcinoma (pCCA) frequently presents as an indeterminate perihilar biliary stricture. The diagnosis is often delayed or uncertain because of the limited sensitivity of conventional endobiliary sampling and blood-based markers, especially in patients with additional confounding conditions such as primary sclerosing cholangitis (PSC). This diagnostic ambiguity can significantly impact clinical outcomes as timely detection and accurate classification are critical for referral and curative-intent treatment. As such, research focused on advancing diagnostic methodologies is a priority. pCCA has a distinct proteomic signature, pattern of activated signaling cascades, epigenetic modifications, and metabolic interactions within its anatomic niche. Recent advances in omics-based diagnostics have leveraged these biological features to identify biomarkers for accurate pCCA diagnosis. In this review, we summarize emerging evidence for omics-based diagnostics in pCCA using clinically accessible samples, including biliary brushings, bile and serum\/plasma samples. We discuss the key aspects of pCCA biology that form the foundation for development of novel techniques including glyco-\/phospho-\/proteomic, genomic, methylomic, metabolomic, and lipidomic analyses as well as multiomic approaches. We conclude by outlining how artificial intelligence may help integrate the data into diagnostic algorithms and identifying areas requiring further investigation to advance these diagnostics into routine clinical practice.<\/jats:p>","DOI":"10.1007\/s00535-026-02453-x","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T16:58:23Z","timestamp":1781283503000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging omics diagnosis of perihilar cholangiocarcinoma"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-305X","authenticated-orcid":false,"given":"Enis Hikmet","family":"Ozmert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby Kohatsu","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumera Irie","family":"Ilyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory Lane","family":"Smoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory James","family":"Gores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"2453_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092208","author":"DB Hewitt","year":"2022","unstructured":"Hewitt DB, Brown ZJ, Pawlik TM. Current perspectives on the surgical management of perihilar cholangiocarcinoma. Cancers (Basel). 2022. https:\/\/doi.org\/10.3390\/cancers14092208.","journal-title":"Cancers (Basel)"},{"key":"2453_CR2","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","volume":"17","author":"JM Banales","year":"2020","unstructured":"Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557\u201388. https:\/\/doi.org\/10.1038\/s41575-020-0310-z.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2453_CR3","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1111\/liv.14856","volume":"41","author":"AM van Keulen","year":"2021","unstructured":"van Keulen AM, Franssen S, van der Geest LG, et al. Nationwide treatment and outcomes of perihilar cholangiocarcinoma. Liver Int. 2021;41:1945\u201353. https:\/\/doi.org\/10.1111\/liv.14856.","journal-title":"Liver Int"},{"key":"2453_CR4","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1097\/SLA.0000000000003801","volume":"273","author":"WA Cambridge","year":"2021","unstructured":"Cambridge WA, Fairfield C, Powell JJ, et al. Meta-analysis and meta-regression of survival after liver transplantation for unresectable perihilar cholangiocarcinoma. Ann Surg. 2021;273:240\u201350. https:\/\/doi.org\/10.1097\/SLA.0000000000003801.","journal-title":"Ann Surg"},{"key":"2453_CR5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41575-025-01153-w","volume":"23","author":"JM Banales","year":"2026","unstructured":"Banales JM, Rodrigues PM, Affo S, et al. Cholangiocarcinoma 2026: status quo, unmet needs and priorities. Nat Rev Gastroenterol Hepatol. 2026;23:65\u201396. https:\/\/doi.org\/10.1038\/s41575-025-01153-w.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2453_CR6","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/hpb.12450","volume":"17","author":"JC Mansour","year":"2015","unstructured":"Mansour JC, Aloia TA, Crane CH, et al. Hilar cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17:691\u20139. https:\/\/doi.org\/10.1111\/hpb.12450.","journal-title":"HPB (Oxford)"},{"issue":"Suppl 1","key":"2453_CR7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/liv.14093","volume":"39","author":"T Kendall","year":"2019","unstructured":"Kendall T, Verheij J, Gaudio E, et al. Anatomical, histomorphological and molecular classification of cholangiocarcinoma. Liver Int. 2019;39(Suppl 1):7\u201318. https:\/\/doi.org\/10.1111\/liv.14093.","journal-title":"Liver Int"},{"key":"2453_CR8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.14309\/ajg.0000000000002190","volume":"118","author":"BJ Elmunzer","year":"2023","unstructured":"Elmunzer BJ, Maranki JL, Gomez V, et al. ACG clinical guideline: diagnosis and management of biliary strictures. Am J Gastroenterol. 2023;118:405\u201326. https:\/\/doi.org\/10.14309\/ajg.0000000000002190.","journal-title":"Am J Gastroenterol"},{"key":"2453_CR9","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1002\/hep.32771","volume":"77","author":"CL Bowlus","year":"2023","unstructured":"Bowlus CL, Arrive L, Bergquist A, et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2023;77:659\u2013702. https:\/\/doi.org\/10.1002\/hep.32771.","journal-title":"Hepatology"},{"key":"2453_CR10","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000751","author":"M Aggarwal","year":"2025","unstructured":"Aggarwal M, Gores GJ, Vargas EJ, et al. The incidence and predictors of false-negative pancreatobiliary fluorescence in situ hybridization (PB-FISH) in biliary strictures: a prospective study. Hepatol Commun. 2025. https:\/\/doi.org\/10.1097\/HC9.0000000000000751.","journal-title":"Hepatol Commun"},{"key":"2453_CR11","doi-asserted-by":"publisher","DOI":"10.1155\/cjgh\/8465615","volume":"2025","author":"Y Liu","year":"2025","unstructured":"Liu Y, Zhang J, Zheng Z, et al. The interplay between CA19-9 and the Lewis blood group system: implications for the diagnosis of gallbladder cancer. Can J Gastroenterol Hepatol. 2025;2025:8465615. https:\/\/doi.org\/10.1155\/cjgh\/8465615.","journal-title":"Can J Gastroenterol Hepatol"},{"key":"2453_CR12","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.jhep.2025.03.007","volume":"83","author":"European Association for the Study of the L","year":"2025","unstructured":"European Association for the Study of the L. EASL clinical practice guidelines on the management of extrahepatic cholangiocarcinoma. J Hepatol. 2025;83:211\u201338. https:\/\/doi.org\/10.1016\/j.jhep.2025.03.007.","journal-title":"J Hepatol"},{"key":"2453_CR13","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.gie.2013.09.015","volume":"79","author":"G Trikudanathan","year":"2014","unstructured":"Trikudanathan G, Navaneethan U, Njei B, et al. Diagnostic yield of bile duct brushings for cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis. Gastrointest Endosc. 2014;79:783\u20139. https:\/\/doi.org\/10.1016\/j.gie.2013.09.015.","journal-title":"Gastrointest Endosc"},{"key":"2453_CR14","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1002\/cld.328","volume":"3","author":"J Mertens","year":"2014","unstructured":"Mertens J. Clinical diagnosis and management of perihilar cholangiocarcinoma. Clin Liver Dis. 2014;3:60\u20134. https:\/\/doi.org\/10.1002\/cld.328.","journal-title":"Clin Liver Dis"},{"key":"2453_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpb.2025.12.012","author":"JA Fritzsche","year":"2025","unstructured":"Fritzsche JA, Smit E, Ponsioen CY, et al. High sensitivity of biliary brush cytology in patients with suspected perihilar or intrahepatic cholangiocarcinoma: a prospective cohort comparison with historical controls. HPB (Oxford). 2025. https:\/\/doi.org\/10.1016\/j.hpb.2025.12.012.","journal-title":"HPB (Oxford)"},{"key":"2453_CR16","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1053\/j.gastro.2015.08.046","volume":"149","author":"EG Barr Fritcher","year":"2015","unstructured":"Barr Fritcher EG, Voss JS, Brankley SM, et al. An optimized set of fluorescence in situ hybridization probes for detection of pancreatobiliary tract cancer in cytology brush samples. Gastroenterology. 2015;149:1813-24 e1. https:\/\/doi.org\/10.1053\/j.gastro.2015.08.046.","journal-title":"Gastroenterology"},{"key":"2453_CR17","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.12659\/msm.895040","volume":"21","author":"B Liang","year":"2015","unstructured":"Liang B, Zhong L, He Q, et al. Diagnostic accuracy of serum CA19-9 in patients with cholangiocarcinoma: a systematic review and meta-analysis. Med Sci Monit. 2015;21:3555\u201363. https:\/\/doi.org\/10.12659\/msm.895040.","journal-title":"Med Sci Monit"},{"key":"2453_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10071345","author":"JW Lee","year":"2021","unstructured":"Lee JW, Lee JH, Park Y, et al. Prognostic impact of perioperative CA19-9 levels in patients with resected perihilar cholangiocarcinoma. J Clin Med. 2021. https:\/\/doi.org\/10.3390\/jcm10071345.","journal-title":"J Clin Med"},{"key":"2453_CR19","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/14737159.2025.2521538","volume":"25","author":"A Stenzinger","year":"2025","unstructured":"Stenzinger A, Normanno N, Lamarca A, et al. From barriers to solutions: an expert-based algorithm for cholangiocarcinoma and other biliary tract cancers testing in the era of precision oncology. Expert Rev Mol Diagn. 2025;25:495\u2013508. https:\/\/doi.org\/10.1080\/14737159.2025.2521538.","journal-title":"Expert Rev Mol Diagn"},{"key":"2453_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800128","volume":"13","author":"J Le Faouder","year":"2019","unstructured":"Le Faouder J, Gigante E, Leger T, et al. Proteomic landscape of cholangiocarcinomas reveals three different subgroups according to their localization and the aspect of non-tumor liver. Proteomics Clin Appl. 2019;13:e1800128. https:\/\/doi.org\/10.1002\/prca.201800128.","journal-title":"Proteomics Clin Appl"},{"key":"2453_CR21","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jhep.2009.03.017","volume":"51","author":"N Guedj","year":"2009","unstructured":"Guedj N, Zhan Q, Perigny M, et al. Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas. J Hepatol. 2009;51:93\u2013101. https:\/\/doi.org\/10.1016\/j.jhep.2009.03.017.","journal-title":"J Hepatol"},{"key":"2453_CR22","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1002\/jhbp.262","volume":"22","author":"S Maeda","year":"2015","unstructured":"Maeda S, Morikawa T, Takadate T, et al. Mass spectrometry-based proteomic analysis of formalin-fixed paraffin-embedded extrahepatic cholangiocarcinoma. J Hepato-Biliary-Pancreat Sci. 2015;22:683\u201391. https:\/\/doi.org\/10.1002\/jhbp.262.","journal-title":"J Hepato-Biliary-Pancreat Sci"},{"key":"2453_CR23","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1093\/gastro\/gou066","volume":"3","author":"U Navaneethan","year":"2015","unstructured":"Navaneethan U, Lourdusamy V, Gk Venkatesh P, et al. Bile proteomics for differentiation of malignant from benign biliary strictures: a pilot study. Gastroenterol Rep (Oxf). 2015;3:136\u201343. https:\/\/doi.org\/10.1093\/gastro\/gou066.","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"2453_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109583","volume":"121","author":"R Sun","year":"2020","unstructured":"Sun R, Chen T, Li M, et al. PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation. Biomed Pharmacother. 2020;121:109583. https:\/\/doi.org\/10.1016\/j.biopha.2019.109583.","journal-title":"Biomed Pharmacother"},{"key":"2453_CR25","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/hep.32624","volume":"77","author":"M Deng","year":"2023","unstructured":"Deng M, Ran P, Chen L, et al. Proteogenomic characterization of cholangiocarcinoma. Hepatology. 2023;77:411\u201329. https:\/\/doi.org\/10.1002\/hep.32624.","journal-title":"Hepatology"},{"key":"2453_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193088","author":"Y Lu","year":"2022","unstructured":"Lu Y, Li X, Zhao K, et al. Proteomic and phosphoproteomic profiling reveals the oncogenic role of Protein Kinase D family kinases in cholangiocarcinoma. Cells. 2022. https:\/\/doi.org\/10.3390\/cells11193088.","journal-title":"Cells"},{"key":"2453_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2025.101084","volume":"24","author":"Z Xia","year":"2025","unstructured":"Xia Z, Gao L, Hu M, et al. Comparative N-Glycoproteomics reveals subtype-specific N-Glycosylation signatures and immune associations in cholangiocarcinoma. Mol Cell Proteom. 2025;24:101084. https:\/\/doi.org\/10.1016\/j.mcpro.2025.101084.","journal-title":"Mol Cell Proteom"},{"key":"2453_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10110460","author":"TT Chang","year":"2018","unstructured":"Chang TT, Tsai HW, Ho CH. Fucosyl-Agalactosyl IgG(1) induces cholangiocarcinoma metastasis and early recurrence by activating tumor-associated macrophage. Cancers (Basel). 2018. https:\/\/doi.org\/10.3390\/cancers10110460.","journal-title":"Cancers (Basel)"},{"key":"2453_CR29","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s00418-024-02270-4","volume":"161","author":"W Phuyathip","year":"2024","unstructured":"Phuyathip W, Putthisen S, Panawan O, et al. Role of Wisteria floribunda agglutinin binding glycans in carcinogenesis and metastasis of cholangiocarcinoma. Histochem Cell Biol. 2024;161:423\u201334. https:\/\/doi.org\/10.1007\/s00418-024-02270-4.","journal-title":"Histochem Cell Biol"},{"key":"2453_CR30","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1002\/ueg2.70054","volume":"13","author":"LJ Chu","year":"2025","unstructured":"Chu LJ, Tsai CJ, Chien CC, et al. Plasma POSTN derived from bile proteome is a promising biomarker for cholangiocarcinoma with efficacy comparable and complementary to CA19.9. United Eur Gastroenterol J. 2025;13:1155\u201370. https:\/\/doi.org\/10.1002\/ueg2.70054.","journal-title":"United Eur Gastroenterol J"},{"key":"2453_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-023-02990-9","volume":"21","author":"L Gao","year":"2023","unstructured":"Gao L, Lin Y, Yue P, et al. Identification of a novel bile marker clusterin and a public online prediction platform based on deep learning for cholangiocarcinoma. BMC Med. 2023;21:294. https:\/\/doi.org\/10.1186\/s12916-023-02990-9.","journal-title":"BMC Med"},{"key":"2453_CR32","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1111\/jgh.12247","volume":"28","author":"Y Sato","year":"2013","unstructured":"Sato Y, Harada K, Sasaki M, et al. Clinicopathological significance of S100 protein expression in cholangiocarcinoma. J Gastroenterol Hepatol. 2013;28:1422\u20139. https:\/\/doi.org\/10.1111\/jgh.12247.","journal-title":"J Gastroenterol Hepatol"},{"key":"2453_CR33","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/hep.29291","volume":"66","author":"A Arbelaiz","year":"2017","unstructured":"Arbelaiz A, Azkargorta M, Krawczyk M, et al. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2017;66:1125\u201343. https:\/\/doi.org\/10.1002\/hep.29291.","journal-title":"Hepatology"},{"key":"2453_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81023-y","volume":"11","author":"C Ikeda","year":"2021","unstructured":"Ikeda C, Haga H, Makino N, et al. Utility of Claudin-3 in extracellular vesicles from human bile as biomarkers of cholangiocarcinoma. Sci Rep. 2021;11:1195. https:\/\/doi.org\/10.1038\/s41598-021-81023-y.","journal-title":"Sci Rep"},{"key":"2453_CR35","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1002\/cncr.20469","volume":"101","author":"J Koopmann","year":"2004","unstructured":"Koopmann J, Thuluvath PJ, Zahurak ML, et al. Mac-2-binding protein is a diagnostic marker for biliary tract carcinoma. Cancer. 2004;101:1609\u201315. https:\/\/doi.org\/10.1002\/cncr.20469.","journal-title":"Cancer"},{"key":"2453_CR36","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1002\/hep.24103","volume":"53","author":"TO Lankisch","year":"2011","unstructured":"Lankisch TO, Metzger J, Negm AA, et al. Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis. Hepatology. 2011;53:875\u201384. https:\/\/doi.org\/10.1002\/hep.24103.","journal-title":"Hepatology"},{"key":"2453_CR37","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1136\/gutjnl-2012-302047","volume":"62","author":"J Metzger","year":"2013","unstructured":"Metzger J, Negm AA, Plentz RR, et al. Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders. Gut. 2013;62:122\u201330. https:\/\/doi.org\/10.1136\/gutjnl-2012-302047.","journal-title":"Gut"},{"key":"2453_CR38","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1177\/2050640616687836","volume":"5","author":"T Voigtlander","year":"2017","unstructured":"Voigtlander T, Metzger J, Schonemeier B, et al. A combined bile and urine proteomic test for cholangiocarcinoma diagnosis in patients with biliary strictures of unknown origin. United Eur Gastroenterol J. 2017;5:668\u201376. https:\/\/doi.org\/10.1177\/2050640616687836.","journal-title":"United Eur Gastroenterol J"},{"key":"2453_CR39","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.7314\/apjcp.2015.16.3.1011","volume":"16","author":"K Kotawong","year":"2015","unstructured":"Kotawong K, Thitapakorn V, Roytrakul S, et al. Plasma phosphoproteome and differential plasma phosphoproteins with Opisthorchis viverrini-related cholangiocarcinoma. Asian Pac J Cancer Prev. 2015;16:1011\u20138. https:\/\/doi.org\/10.7314\/apjcp.2015.16.3.1011.","journal-title":"Asian Pac J Cancer Prev"},{"key":"2453_CR40","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1017\/S0031182021001694","volume":"149","author":"S Prasopdee","year":"2022","unstructured":"Prasopdee S, Yingchutrakul Y, Roytrakul S, et al. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta as a potential biomarker for Opisthorchis viverrini infection and cholangiocarcinoma. Parasitology. 2022;149:171\u201380. https:\/\/doi.org\/10.1017\/S0031182021001694.","journal-title":"Parasitology"},{"key":"2453_CR41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1007\/s00535-016-1230-0","volume":"52","author":"J Shoda","year":"2017","unstructured":"Shoda J, Matsuda A, Shida T, et al. Wisteria floribunda agglutinin-sialylated mucin core polypeptide 1 is a sensitive biomarker for biliary tract carcinoma and intrahepatic cholangiocarcinoma: a multicenter study. J Gastroenterol. 2017;52:218\u201328. https:\/\/doi.org\/10.1007\/s00535-016-1230-0.","journal-title":"J Gastroenterol"},{"key":"2453_CR42","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.cca.2022.09.012","volume":"536","author":"P Kimawaha","year":"2022","unstructured":"Kimawaha P, Thanan R, Jusakul A, et al. Serum \u03b12,6-sialylated glycoform of serotransferrin as a glycobiomarker for diagnosis and prediction of clinical severity in cholangiocarcinoma. Clin Chim Acta. 2022;536:142\u201354. https:\/\/doi.org\/10.1016\/j.cca.2022.09.012.","journal-title":"Clin Chim Acta"},{"key":"2453_CR43","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.cca.2020.07.017","volume":"510","author":"A Silsirivanit","year":"2020","unstructured":"Silsirivanit A, Matsuda A, Kuno A, et al. Multi-serum glycobiomarkers improves the diagnosis and prognostic prediction of cholangiocarcinoma. Clin Chim Acta. 2020;510:142\u20139. https:\/\/doi.org\/10.1016\/j.cca.2020.07.017.","journal-title":"Clin Chim Acta"},{"key":"2453_CR44","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1111\/cas.12222","volume":"104","author":"A Silsirivanit","year":"2013","unstructured":"Silsirivanit A, Araki N, Wongkham C, et al. CA-S27: a novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma. Cancer Sci. 2013;104:1278\u201384. https:\/\/doi.org\/10.1111\/cas.12222.","journal-title":"Cancer Sci"},{"key":"2453_CR45","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201600141","author":"L Betesh","year":"2017","unstructured":"Betesh L, Comunale MA, Wang M, et al. Identification of fucosylated Fetuin-A as a potential biomarker for cholangiocarcinoma. Proteom Clin Appl. 2017. https:\/\/doi.org\/10.1002\/prca.201600141.","journal-title":"Proteom Clin Appl"},{"key":"2453_CR46","doi-asserted-by":"publisher","first-page":"403","DOI":"10.6004\/jnccn.2025.0042","volume":"23","author":"AB Benson","year":"2025","unstructured":"Benson AB, D\u2019Angelica MI, Abrams T. Biliary tract cancers, Version 2.2025, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2025;23:403. https:\/\/doi.org\/10.6004\/jnccn.2025.0042.","journal-title":"J Natl Compr Canc Netw"},{"key":"2453_CR47","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s00428-009-0829-4","volume":"455","author":"BH Kim","year":"2009","unstructured":"Kim BH, Cho NY, Shin SH, et al. CpG island hypermethylation and repetitive DNA hypomethylation in premalignant lesion of extrahepatic cholangiocarcinoma. Vir Arch. 2009;455:343\u201351. https:\/\/doi.org\/10.1007\/s00428-009-0829-4.","journal-title":"Vir Arch"},{"key":"2453_CR48","doi-asserted-by":"publisher","first-page":"923","DOI":"10.5858\/2007-131-923-MPOMCI","volume":"131","author":"N-YC Baek-Hee Kim","year":"2007","unstructured":"Baek-Hee Kim N-YC, Minhee C, Sun L, Ja JJ, Gyeong HK. Methylation profiles of multiple CpG Island loci in extrahepatic cholangiocarcinoma versus those of intrahepatic cholangiocarcinomas. Arch Pathol Lab Med. 2007;131:923\u201330.","journal-title":"Arch Pathol Lab Med"},{"key":"2453_CR49","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1002\/hep.26721","volume":"59","author":"B Goeppert","year":"2014","unstructured":"Goeppert B, Konermann C, Schmidt CR, et al. Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway. Hepatology. 2014;59:544\u201354. https:\/\/doi.org\/10.1002\/hep.26721.","journal-title":"Hepatology"},{"key":"2453_CR50","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s10147-020-01846-z","volume":"26","author":"F Feng","year":"2021","unstructured":"Feng F, Wu X, Shi X, et al. Comprehensive analysis of genomic alterations of Chinese hilar cholangiocarcinoma patients. Int J Clin Oncol. 2021;26:717\u201327. https:\/\/doi.org\/10.1007\/s10147-020-01846-z.","journal-title":"Int J Clin Oncol"},{"key":"2453_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30708-7","volume":"13","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Ma Z, Li C, et al. The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers. Nat Commun. 2022;13:3061. https:\/\/doi.org\/10.1038\/s41467-022-30708-7.","journal-title":"Nat Commun"},{"key":"2453_CR52","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","volume":"397","author":"JW Valle","year":"2021","unstructured":"Valle JW, Kelley RK, Nervi B, et al. Biliary tract cancer. Lancet. 2021;397:428\u201344. https:\/\/doi.org\/10.1016\/S0140-6736(21)00153-7.","journal-title":"Lancet"},{"key":"2453_CR53","doi-asserted-by":"publisher","DOI":"10.1200\/PO.24.00206","volume":"8","author":"WA Preston","year":"2024","unstructured":"Preston WA, Drill E, Boerner T, et al. Extrahepatic cholangiocarcinoma: genomic variables associated with anatomic location and outcome. JCO Precis Oncol. 2024;8:e2400206. https:\/\/doi.org\/10.1200\/PO.24.00206.","journal-title":"JCO Precis Oncol"},{"key":"2453_CR54","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.jhep.2020.03.008","volume":"73","author":"R Montal","year":"2020","unstructured":"Montal R, Sia D, Montironi C, et al. Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J Hepatol. 2020;73:315\u201327. https:\/\/doi.org\/10.1016\/j.jhep.2020.03.008.","journal-title":"J Hepatol"},{"key":"2453_CR55","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/modpathol.3800287","volume":"18","author":"B Yang","year":"2005","unstructured":"Yang B, House MG, Guo M, et al. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol. 2005;18:412\u201320. https:\/\/doi.org\/10.1038\/modpathol.3800287.","journal-title":"Mod Pathol"},{"key":"2453_CR56","first-page":"1773","volume":"9","author":"C-JH Bodo-Klump","year":"2003","unstructured":"Bodo-Klump C-JH, Stephan D, Karlheinz HRK, Michael JUS, Marianne O, et al. Promoter methylation of INK4a\/ARF as detected in bilesignificance for the differential diagnosis in biliary disease. Clin Cancer Res. 2003;9:1773\u20138.","journal-title":"Clin Cancer Res"},{"key":"2453_CR57","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.clinbiochem.2010.08.013","volume":"43","author":"Y Zhang","year":"2010","unstructured":"Zhang Y, Yang B, Du Z, et al. Identification and validation of specific methylation profile in bile for differential diagnosis of malignant biliary stricture. Clin Biochem. 2010;43:1340\u20134. https:\/\/doi.org\/10.1016\/j.clinbiochem.2010.08.013.","journal-title":"Clin Biochem"},{"key":"2453_CR58","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1478-3231.2007.01624.x","volume":"28","author":"DS Sandhu","year":"2008","unstructured":"Sandhu DS, Shire AM, Roberts LR. Epigenetic DNA hypermethylation in cholangiocarcinoma: potential roles in pathogenesis, diagnosis and identification of treatment targets. Liver Int. 2008;28:12\u201327. https:\/\/doi.org\/10.1111\/j.1478-3231.2007.01624.x.","journal-title":"Liver Int"},{"key":"2453_CR59","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1245\/ASO.2005.07.020","volume":"12","author":"Y Koga","year":"2005","unstructured":"Koga Y, Kitajima Y, Miyoshi A, et al. Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers. Ann Surg Oncol. 2005;12:354\u201363. https:\/\/doi.org\/10.1245\/ASO.2005.07.020.","journal-title":"Ann Surg Oncol"},{"key":"2453_CR60","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1002\/1878-0261.13256","volume":"16","author":"M Niger","year":"2022","unstructured":"Niger M, Nichetti F, Casadei-Gardini A, et al. MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers. Mol Oncol. 2022;16:2733\u201346. https:\/\/doi.org\/10.1002\/1878-0261.13256.","journal-title":"Mol Oncol"},{"key":"2453_CR61","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1111\/j.1349-7006.2004.tb03254.x","volume":"95","author":"T Tozawa","year":"2004","unstructured":"Tozawa T, Tamura G, Honda T, et al. Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients. Cancer Sci. 2004;95:736\u201340. https:\/\/doi.org\/10.1111\/j.1349-7006.2004.tb03254.x.","journal-title":"Cancer Sci"},{"key":"2453_CR62","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1177\/1533034617748090","volume":"16","author":"V Prachayakul","year":"2017","unstructured":"Prachayakul V, Kanchanapermpoon J, Thuwajit C, et al. DNA methylation markers improve the sensitivity of endoscopic retrograde cholangiopancreatography-based brushing cytology in extrahepatic cholangiocarcinoma. Technol Cancer Res Treat. 2017;16:1252\u20138. https:\/\/doi.org\/10.1177\/1533034617748090.","journal-title":"Technol Cancer Res Treat"},{"key":"2453_CR63","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1158\/1940-6207.CAPR-13-0104","volume":"6","author":"R Sriraksa","year":"2013","unstructured":"Sriraksa R, Zeller C, Dai W, et al. Aberrant DNA methylation at genes associated with a stem cell-like phenotype in cholangiocarcinoma tumors. Cancer Prev Res (Phila). 2013;6:1348\u201355. https:\/\/doi.org\/10.1158\/1940-6207.CAPR-13-0104.","journal-title":"Cancer Prev Res (Phila)"},{"key":"2453_CR64","doi-asserted-by":"publisher","first-page":"481","DOI":"10.2217\/epi-2021-0343","volume":"14","author":"AC Cheung","year":"2022","unstructured":"Cheung AC, Juran BD, Schlicht EM, et al. DNA methylation profile of liver tissue in end-stage cholestatic liver disease. Epigenomics. 2022;14:481\u201397. https:\/\/doi.org\/10.2217\/epi-2021-0343.","journal-title":"Epigenomics"},{"key":"2453_CR65","doi-asserted-by":"publisher","first-page":"4054","DOI":"10.1111\/cas.16365","volume":"115","author":"S Ito","year":"2024","unstructured":"Ito S, Ando M, Aoki S, et al. Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers. Cancer Sci. 2024;115:4054\u201363. https:\/\/doi.org\/10.1111\/cas.16365.","journal-title":"Cancer Sci"},{"key":"2453_CR66","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13010039","author":"C Driescher","year":"2020","unstructured":"Driescher C, Fuchs K, Haeberle L, et al. Bile-based cell-free DNA analysis is a reliable diagnostic tool in pancreatobiliary cancer. Cancers (Basel). 2020. https:\/\/doi.org\/10.3390\/cancers13010039.","journal-title":"Cancers (Basel)"},{"key":"2453_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.961939","volume":"12","author":"Z Li","year":"2022","unstructured":"Li Z, Liu Y, Fu J, et al. Bile is a reliable and valuable source to study cfDNA in biliary tract cancers. Front Oncol. 2022;12:961939. https:\/\/doi.org\/10.3389\/fonc.2022.961939.","journal-title":"Front Oncol"},{"key":"2453_CR68","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1136\/gutjnl-2018-317817","volume":"69","author":"AD Singhi","year":"2020","unstructured":"Singhi AD, Nikiforova MN, Chennat J, et al. Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures. Gut. 2020;69:52\u201361. https:\/\/doi.org\/10.1136\/gutjnl-2018-317817.","journal-title":"Gut"},{"key":"2453_CR69","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.gie.2024.12.024","volume":"102","author":"O Bardhi","year":"2025","unstructured":"Bardhi O, Jones A, Ellis D, et al. Next-generation sequencing improves the detection of malignant biliary strictures and changes management. Gastrointest Endosc. 2025;102:56-63 e1. https:\/\/doi.org\/10.1016\/j.gie.2024.12.024.","journal-title":"Gastrointest Endosc"},{"key":"2453_CR70","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1136\/gutjnl-2021-325178","volume":"71","author":"M Arechederra","year":"2022","unstructured":"Arechederra M, Rullan M, Amat I, et al. Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures. Gut. 2022;71:1141\u201351. https:\/\/doi.org\/10.1136\/gutjnl-2021-325178.","journal-title":"Gut"},{"key":"2453_CR71","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.annonc.2022.09.150","volume":"33","author":"JE Berchuck","year":"2022","unstructured":"Berchuck JE, Facchinetti F, DiToro DF, et al. The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer. Ann Oncol. 2022;33:1269\u201383. https:\/\/doi.org\/10.1016\/j.annonc.2022.09.150.","journal-title":"Ann Oncol"},{"key":"2453_CR72","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.jhep.2024.10.020","volume":"82","author":"S Hwang","year":"2025","unstructured":"Hwang S, Woo S, Kang B, et al. Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer. J Hepatol. 2025;82:649\u201357. https:\/\/doi.org\/10.1016\/j.jhep.2024.10.020.","journal-title":"J Hepatol"},{"key":"2453_CR73","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1002\/cncr.34717","volume":"129","author":"H Ohyama","year":"2023","unstructured":"Ohyama H, Hirotsu Y, Amemiya K, et al. Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile. Cancer. 2023;129:1714\u201322. https:\/\/doi.org\/10.1002\/cncr.34717.","journal-title":"Cancer"},{"key":"2453_CR74","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.gie.2021.07.005","volume":"95","author":"V Prachayakul","year":"2022","unstructured":"Prachayakul V, Rugivarodom M, Nopjaroonsri P, et al. Diagnostic power of DNA methylation markers suggestive of cholangiocarcinoma in ERCP-based brush cytology. Gastrointest Endosc. 2022;95:123-30 e1. https:\/\/doi.org\/10.1016\/j.gie.2021.07.005.","journal-title":"Gastrointest Endosc"},{"key":"2453_CR75","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1002\/hep4.1730","volume":"5","author":"JD Yang","year":"2021","unstructured":"Yang JD, Ghoz H, Aboelsoud MM, et al. DNA methylation markers for detection of cholangiocarcinoma: discovery, validation, and clinical testing in biliary brushings and plasma. Hepatol Commun. 2021;5:1448\u201359. https:\/\/doi.org\/10.1002\/hep4.1730.","journal-title":"Hepatol Commun"},{"key":"2453_CR76","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.jmoldx.2012.01.014","volume":"14","author":"SH Shin","year":"2012","unstructured":"Shin SH, Lee K, Kim BH, et al. Bile-based detection of extrahepatic cholangiocarcinoma with quantitative DNA methylation markers and its high sensitivity. J Mol Diagn. 2012;14:256\u201363. https:\/\/doi.org\/10.1016\/j.jmoldx.2012.01.014.","journal-title":"J Mol Diagn"},{"key":"2453_CR77","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1002\/hep.27707","volume":"61","author":"K Andresen","year":"2015","unstructured":"Andresen K, Boberg KM, Vedeld HM, et al. Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma. Hepatology. 2015;61:1651\u20139. https:\/\/doi.org\/10.1002\/hep.27707.","journal-title":"Hepatology"},{"key":"2453_CR78","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13148-019-0634-0","volume":"11","author":"W Wasenang","year":"2019","unstructured":"Wasenang W, Chaiyarit P, Proungvitaya S, et al. Serum cell-free DNA methylation of OPCML and HOXD9 as a biomarker that may aid in differential diagnosis between cholangiocarcinoma and other biliary diseases. Clin Epigenetics. 2019;11:39\u201339. https:\/\/doi.org\/10.1186\/s13148-019-0634-0.","journal-title":"Clin Epigenetics"},{"key":"2453_CR79","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v17.i4.104253","volume":"17","author":"J Yu","year":"2025","unstructured":"Yu J, Liu QC, Lu SY, et al. Detecting plasma SHOX2, HOXA9, SEPTIN9, and RASSF1A methylation and circulating cancer cells for cholangiocarcinoma clinical diagnosis and monitoring. World J Gastrointest Oncol. 2025;17:104253. https:\/\/doi.org\/10.4251\/wjgo.v17.i4.104253.","journal-title":"World J Gastrointest Oncol"},{"key":"2453_CR80","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1515\/hsz-2018-0441","volume":"400","author":"M Prescher","year":"2019","unstructured":"Prescher M, Kroll T, Schmitt L. ABCB4\/MDR3 in health and disease - at the crossroads of biochemistry and medicine. Biol Chem. 2019;400:1245\u201359. https:\/\/doi.org\/10.1515\/hsz-2018-0441.","journal-title":"Biol Chem"},{"key":"2453_CR81","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1248\/cpb.c18-01029","volume":"67","author":"YI Shin-Ya-Morita","year":"2019","unstructured":"Shin-Ya-Morita YI, Tokuji T, Tomohiro T. Molecular mechanisms for protection of hepatocytes against bile salt cytotoxicity. Chem Pharmaceut Bull. 2019;67:333\u201340. https:\/\/doi.org\/10.1248\/cpb.c18-01029.","journal-title":"Chem Pharmaceut Bull"},{"key":"2453_CR82","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1038\/s41416-025-03144-9","volume":"133","author":"FS Liu","year":"2025","unstructured":"Liu FS, Liu YY, Zhang SK, et al. Lipidomic profiling of human bile distinguishes cholangiocarcinoma from benign bile duct diseases with high specificity and sensitivity: a prospective descriptive study. Br J Cancer. 2025;133:1565\u201382. https:\/\/doi.org\/10.1038\/s41416-025-03144-9.","journal-title":"Br J Cancer"},{"key":"2453_CR83","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2025.465778","volume":"1746","author":"HJ Yu","year":"2025","unstructured":"Yu HJ, Moon MH. Direct lipid analysis of exosomes in serum by online miniaturized asymmetrical flow field-flow fractionation and electrospray ionization-mass spectrometry: application to extrahepatic cholangiocarcinoma. J Chromatogr A. 2025;1746:465778. https:\/\/doi.org\/10.1016\/j.chroma.2025.465778.","journal-title":"J Chromatogr A"},{"key":"2453_CR84","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103188","author":"PS Tietz-Bogert","year":"2018","unstructured":"Tietz-Bogert PS, Kim M, Cheung A, et al. Metabolomic profiling of portal blood and bile reveals metabolic signatures of Primary Sclerosing Cholangitis. Int J Mol Sci. 2018. https:\/\/doi.org\/10.3390\/ijms19103188.","journal-title":"Int J Mol Sci"},{"key":"2453_CR85","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-27603-6","volume":"13","author":"D Zhang","year":"2023","unstructured":"Zhang D, Zhao G, Sun W, et al. Bile metabolites as diagnostic biomarkers for perihilar cholangiocarcinoma. Sci Rep. 2023;13:3177. https:\/\/doi.org\/10.1038\/s41598-023-27603-6.","journal-title":"Sci Rep"},{"key":"2453_CR86","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/j.1477-2574.2010.00185.x","volume":"12","author":"AW Sharif","year":"2010","unstructured":"Sharif AW, Williams HR, Lampejo T, et al. Metabolic profiling of bile in cholangiocarcinoma using in vitro magnetic resonance spectroscopy. HPB (Oxford). 2010;12:396\u2013402. https:\/\/doi.org\/10.1111\/j.1477-2574.2010.00185.x.","journal-title":"HPB (Oxford)"},{"key":"2453_CR87","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29445-z","volume":"8","author":"WS Song","year":"2018","unstructured":"Song WS, Park HM, Ha JM, et al. Discovery of glycocholic acid and taurochenodeoxycholic acid as phenotypic biomarkers in cholangiocarcinoma. Sci Rep. 2018;8:11088. https:\/\/doi.org\/10.1038\/s41598-018-29445-z.","journal-title":"Sci Rep"},{"key":"2453_CR88","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2023.117235","volume":"541","author":"X Gui","year":"2023","unstructured":"Gui X, Zhang X, Xin Y, et al. Identification and validation of volatile organic compounds in bile for differential diagnosis of perihilar cholangiocarcinoma. Clin Chim Acta. 2023;541:117235. https:\/\/doi.org\/10.1016\/j.cca.2023.117235.","journal-title":"Clin Chim Acta"},{"key":"2453_CR89","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2020.105775","volume":"205","author":"X Zhang","year":"2021","unstructured":"Zhang X, Yang Z, Shi Z, et al. Analysis of bile acid profile in plasma to differentiate cholangiocarcinoma from benign biliary diseases and healthy controls. J Steroid Biochem Mol Biol. 2021;205:105775. https:\/\/doi.org\/10.1016\/j.jsbmb.2020.105775.","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2453_CR90","doi-asserted-by":"publisher","first-page":"13007","DOI":"10.1002\/cam4.5973","volume":"12","author":"R Muraki","year":"2023","unstructured":"Muraki R, Morita Y, Ida S, et al. Phosphatidylcholine in bile-derived small extracellular vesicles as a novel biomarker of cholangiocarcinoma. Cancer Med. 2023;12:13007\u201318. https:\/\/doi.org\/10.1002\/cam4.5973.","journal-title":"Cancer Med"},{"key":"2453_CR91","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41416-022-02048-2","volume":"128","author":"G Chen","year":"2023","unstructured":"Chen G, Zhang J, Fu Q, et al. Integrative analysis of multi-omics data for liquid biopsy. Br J Cancer. 2023;128:505\u201318. https:\/\/doi.org\/10.1038\/s41416-022-02048-2.","journal-title":"Br J Cancer"},{"key":"2453_CR92","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061644","author":"JM Urman","year":"2020","unstructured":"Urman JM, Herranz JM, Uriarte I, et al. Pilot multi-omic analysis of human bile from benign and malignant biliary strictures: a machine-learning approach. Cancers (Basel). 2020. https:\/\/doi.org\/10.3390\/cancers12061644.","journal-title":"Cancers (Basel)"},{"key":"2453_CR93","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000786","author":"JY Xia","year":"2025","unstructured":"Xia JY, Komanduri S, Keswani RN, et al. Integrating multi-omics in bile for biomarker discovery in cholangiocarcinoma. Hepatol Commun. 2025. https:\/\/doi.org\/10.1097\/HC9.0000000000000786.","journal-title":"Hepatol Commun"},{"key":"2453_CR94","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101736","volume":"55","author":"S He","year":"2023","unstructured":"He S, Zeng F, Yin H, et al. Molecular diagnosis of pancreatobiliary tract cancer by detecting mutations and methylation changes in bile samples. EClinicalMedicine. 2023;55:101736. https:\/\/doi.org\/10.1016\/j.eclinm.2022.101736.","journal-title":"EClinicalMedicine"},{"key":"2453_CR95","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1021\/acs.jproteome.2c00846","volume":"22","author":"X Qu","year":"2023","unstructured":"Qu X, He B, Li Z, et al. Accurate discrimination of benign biliary diseases and cholangiocarcinoma with serum multiomics revealed by high-throughput nanoassisted laser desorption ionization mass spectrometry. J Proteome Res. 2023;22:1855\u201367. https:\/\/doi.org\/10.1021\/acs.jproteome.2c00846.","journal-title":"J Proteome Res"},{"key":"2453_CR96","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1111\/jgh.16180","volume":"38","author":"B Njei","year":"2023","unstructured":"Njei B, Kanmounye US, Seto N, et al. Artificial intelligence in medical imaging for cholangiocarcinoma diagnosis: a systematic review with scientometric analysis. J Gastroenterol Hepatol. 2023;38:874\u201382. https:\/\/doi.org\/10.1111\/jgh.16180.","journal-title":"J Gastroenterol Hepatol"},{"key":"2453_CR97","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/hep.0000000000001314","volume":"83","author":"Y Singh","year":"2026","unstructured":"Singh Y, Eaton JE, Venkatesh SK, et al. Deep learning analysis of MRI accurately detects early-stage perihilar cholangiocarcinoma in patients with primary sclerosing cholangitis. Hepatology. 2026;83:30\u20139. https:\/\/doi.org\/10.1097\/hep.0000000000001314.","journal-title":"Hepatology"},{"key":"2453_CR98","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1007\/s00330-023-10108-1","volume":"34","author":"PC Zhan","year":"2024","unstructured":"Zhan PC, Yang T, Zhang Y, et al. Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study. Eur Radiol. 2024;34:1280\u201391. https:\/\/doi.org\/10.1007\/s00330-023-10108-1.","journal-title":"Eur Radiol"},{"key":"2453_CR99","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1111\/liv.14763","volume":"41","author":"H Qin","year":"2021","unstructured":"Qin H, Hu X, Zhang J, et al. Machine-learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection. Liver Int. 2021;41:837\u201350. https:\/\/doi.org\/10.1111\/liv.14763.","journal-title":"Liver Int"},{"key":"2453_CR100","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1632630","volume":"15","author":"X Quan","year":"2025","unstructured":"Quan X, Huang X, Liu J, et al. Preoperative assessment of longitudinal extent in hilar cholangiocarcinoma using noninvasive enhanced MR radiomics: a multicenter study. Front Oncol. 2025;15:1632630. https:\/\/doi.org\/10.3389\/fonc.2025.1632630.","journal-title":"Front Oncol"},{"key":"2453_CR101","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2026.116699","author":"PMG Filis","year":"2026","unstructured":"Filis PMG, Salgkamis D, Tsinakis N, Zerdes I, Pagkalidou E, Manou M, et al. Integrating liquid biopsies and artificial intelligence for early cancer detection: a systematic review and meta-analysis. Eur J Cancer. 2026. https:\/\/doi.org\/10.1016\/j.ejca.2026.116699.","journal-title":"Eur J Cancer"},{"key":"2453_CR102","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001535","author":"DG Mun","year":"2025","unstructured":"Mun DG, Jessen E, Tomlinson JL, et al. Multiomics combined with machine learning defines unique molecular subtypes of cholangiocarcinoma and identifies TNK1 as a therapeutic target. Hepatology. 2025. https:\/\/doi.org\/10.1097\/HEP.0000000000001535.","journal-title":"Hepatology"},{"key":"2453_CR103","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.14218\/JCTH.2023.00118","volume":"11","author":"H Wang","year":"2023","unstructured":"Wang H, Chen J, Zhang X, et al. Expert consensus on pathological diagnosis of intrahepatic cholangiocarcinoma (2022 version). J Clin Transl Hepatol. 2023;11:1553\u201364. https:\/\/doi.org\/10.14218\/JCTH.2023.00118.","journal-title":"J Clin Transl Hepatol"}],"container-title":["Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-026-02453-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00535-026-02453-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-026-02453-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T16:58:25Z","timestamp":1781283505000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00535-026-02453-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":103,"alternative-id":["2453"],"URL":"https:\/\/doi.org\/10.1007\/s00535-026-02453-x","relation":{},"ISSN":["0944-1174","1435-5922"],"issn-type":[{"value":"0944-1174","type":"print"},{"value":"1435-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"assertion":[{"value":"4 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}