{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:29:11Z","timestamp":1760146151350,"version":"build-2065373602"},"reference-count":153,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC.<\/jats:p>","DOI":"10.3390\/cancers16193432","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T07:54:09Z","timestamp":1728546849000},"page":"3432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interplay of Cardiometabolic Syndrome and Biliary Tract Cancer: A Comprehensive Analysis with Gender-Specific Insights"],"prefix":"10.3390","volume":"16","author":[{"given":"Vincenza","family":"Di Stasi","sequence":"first","affiliation":[{"name":"Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Contaldo","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Birtolo","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Umberto I Hospital, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-0436","authenticated-orcid":false,"given":"Endrit","family":"Shahini","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1186\/s13046-022-02536-6","article-title":"Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-\u03b2 inhibition","volume":"41","author":"Mancarella","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1158\/0008-5472.CAN-13-1911","article-title":"Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma","volume":"74","author":"Guest","year":"2014","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jhep.2019.09.007","article-title":"Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis","volume":"72","author":"Clements","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Expert consensus document: Cholangiocarcinoma: Current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","volume":"13","author":"Banales","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/hep.31146","article-title":"Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma","volume":"72","author":"Lavu","year":"2020","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"325","DOI":"10.4166\/kjg.2015.66.6.325","article-title":"Inflammation and Cancer Development in Pancreatic and Biliary Tract Cancer","volume":"66","author":"Lee","year":"2015","journal-title":"Korean J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"289645","DOI":"10.1155\/2010\/289645","article-title":"Chronic Inflammation in Obesity and the Metabolic Syndrome","volume":"2010","author":"Monteiro","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3322\/caac.21499","article-title":"Global patterns in excess body weight and the associated cancer burden","volume":"69","author":"Sung","year":"2019","journal-title":"CA A Cancer J. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.soard.2023.01.025","article-title":"Excess body fatness and cancer risk: A summary of the epidemiologic evidence","volume":"19","author":"Patel","year":"2023","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nrgastro.2011.23","article-title":"Excess body weight and obesity\u2014The link with gastrointestinal and hepatobiliary cancer","volume":"8","author":"Kant","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1158\/0008-5472.CAN-19-0459","article-title":"Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project","volume":"79","author":"Jackson","year":"2019","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9541","DOI":"10.3748\/wjg.v20.i28.9541","article-title":"Association of metabolic syndromes and risk factors with ampullary tumors development: A case-control study in China","volume":"20","author":"He","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/bjc.2011.363","article-title":"Metabolic syndrome and insulin resistance in relation to biliary tract cancer and stone risks: A population-based study in Shanghai, China","volume":"105","author":"Shebl","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/ijc.21683","article-title":"Gallbladder cancer worldwide: Geographical distribution and risk factors","volume":"118","author":"Randi","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.cgh.2007.05.020","article-title":"Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based case-control study","volume":"5","author":"Welzel","year":"2007","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/sj.bjc.6604765","article-title":"The antecedents of biliary cancer: A primary care case\u2013control study in the United Kingdom","volume":"100","author":"Grainge","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s10552-011-9754-3","article-title":"Diabetes mellitus and increased risk of biliary tract cancer: Systematic review and meta-analysis","volume":"22","author":"Ren","year":"2011","journal-title":"Cancer Causes Control."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1093\/annonc\/mdt204","article-title":"Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort","volume":"24","author":"Schlesinger","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154848","DOI":"10.1016\/j.metabol.2021.154848","article-title":"Association of prediabetes, diabetes, and diabetes duration with biliary tract cancer risk: A nationwide cohort study","volume":"123","author":"Park","year":"2021","journal-title":"Metabolism"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Petrick, J.L., Yang, B., Altekruse, S.F., Van Dyke, A.L., Koshiol, J., Graubard, B.I., and McGlynn, K.A. (2017). Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based study in SEER-Medicare. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186643"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/hep.24397","article-title":"Metabolic syndrome increases the risk of primary liver cancer in the United States: A study in the SEER-Medicare database","volume":"54","author":"Welzel","year":"2011","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.2147\/CMAR.S175628","article-title":"Metabolic syndrome and the risk of cholangiocarcinoma: A hospital-based case\u2013control study in China","volume":"10","author":"Xiong","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cadamuro, M., Sarcognato, S., Camerotto, R., Girardi, N., Lasagni, A., Zanus, G., Cillo, U., Gringeri, E., Morana, G., and Strazzabosco, M. (2023). Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054748"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/17474124.2021.1946393","article-title":"Metabolic disorders and the risk of cholangiocarcinoma","volume":"15","author":"Ghidini","year":"2021","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"877","DOI":"10.2353\/ajpath.2006.050464","article-title":"Estrogens and insulin-like growth factor 1 modulate neoplastic cell growth in human cholangiocarcinoma","volume":"169","author":"Alvaro","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/ijc.2910520217","article-title":"Two new human cholangiocarcinoma cell lines and their cytogenetics and responses to growth factors, hormones, cytokines or immunologic effector cells","volume":"52","author":"Shimizu","year":"1992","journal-title":"Int. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xu, L., Hausmann, M., Dietmaier, W., Kellermeier, S., Pesch, T., Stieber-Gunckel, M., Lippert, E., Klebl, F., and Rogler, G. (2010). Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-302"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.amjms.2015.12.013","article-title":"Insulin-Like Growth Factor-1 and Vascular Endothelial Growth Factor in Malignant and Benign Biliary Obstructions","volume":"351","author":"ElMahdy","year":"2016","journal-title":"Am. J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"451","DOI":"10.7326\/0003-4819-147-7-200710020-00003","article-title":"Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis","volume":"147","author":"Alvaro","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.canlet.2004.07.027","article-title":"Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2","volume":"219","author":"Tanimura","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ejca.2021.06.052","article-title":"Persistent status of metabolic syndrome and risk of cholangiocarcinoma: A Korean nationwide population-based cohort study","volume":"155","author":"Park","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3748\/wjg.v19.i4.457","article-title":"Obesity and cholangiocarcinoma","volume":"19","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/jhbp.1001","article-title":"Obesity and cholangiocarcinoma: A review of epidemiological and molecular associations","volume":"28","author":"Osataphan","year":"2021","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: Global epidemiology and pathogenesis","volume":"15","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_38","first-page":"e46400","article-title":"Associations of Liver Fluke Infection and Cholangiocarcinoma: A Scoping Review","volume":"15","author":"Sivanand","year":"2023","journal-title":"Cureus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.steroids.2011.10.013","article-title":"Tissue physiology and pathology of aromatase","volume":"77","author":"Stocco","year":"2012","journal-title":"Steroids"},{"key":"ref_40","first-page":"1743","article-title":"Tamoxifen-mediated growth inhibition of human cholangiocarcinoma","volume":"57","author":"Sampson","year":"1997","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1053\/gast.2000.20184","article-title":"Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats","volume":"119","author":"Alvaro","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/hep.23386","article-title":"Estrogen stimulates female biliary epithelial cell interleukin-6 expression in mice and humans","volume":"51","author":"Isse","year":"2010","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.dld.2008.02.015","article-title":"Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor","volume":"41","author":"Mancino","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41416-020-0835-5","article-title":"Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: Results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank","volume":"123","author":"Petrick","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/hep.31057","article-title":"Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women","volume":"72","author":"Petrick","year":"2020","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1158\/0008-5472.CAN-07-6682","article-title":"Leptin enhances cholangiocarcinoma cell growth","volume":"68","author":"Fava","year":"2008","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.21873\/invivo.12064","article-title":"Role of Leptin in Neoplastic and Biliary Tree Disease","volume":"34","author":"Izzo","year":"2020","journal-title":"In Vivo"},{"key":"ref_48","first-page":"298","article-title":"Leptin stimulates the epithelial-mesenchymal transition and pro-angiogenic capability of cholangiocarcinoma cells through the miR-122\/PKM2 axis","volume":"55","author":"Peng","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1530\/ERC-20-0297","article-title":"Adiponectin receptor activation inhibits prostate cancer xenograft growth","volume":"27","author":"Philp","year":"2020","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Raut, P.K., and Park, P.-H. (2020). Globular adiponectin antagonizes leptin-induced growth of cancer cells by modulating inflammasomes activation: Critical role of HO-1 signaling. Biochem. Pharmacol., 180.","DOI":"10.1016\/j.bcp.2020.114186"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.2174\/0109298673254969231122114107","article-title":"Novel Adiponectin Receptor Agonist Inhibits Cholangiocarcinoma via Adenosine Monophosphate-activated Protein Kinase","volume":"31","author":"Bui","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"108","DOI":"10.5114\/pg.2015.49004","article-title":"Diabetes mellitus and the risk of cholangiocarcinoma: An updated meta-analysis","volume":"10","author":"Li","year":"2015","journal-title":"Prz. Gastroenterol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.canep.2015.04.002","article-title":"Diabetes mellitus: Possible risk and promoting factors of cholangiocarcinoma: Association of diabetes mellitus and cholangiocarcinoma","volume":"39","author":"Saengboonmee","year":"2015","journal-title":"Cancer Epidemiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s41395-018-0207-4","article-title":"Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis","volume":"113","author":"Petrick","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"172","DOI":"10.5009\/gnl.2012.6.2.172","article-title":"Epidemiology of gallbladder disease: Cholelithiasis and cancer","volume":"6","author":"Stinton","year":"2012","journal-title":"Gut Liver"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1056\/NEJMoa021423","article-title":"Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults","volume":"348","author":"Calle","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/sj.bjc.6603703","article-title":"Obesity and the risk of gallbladder cancer: A meta-analysis","volume":"96","author":"Larsson","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wan, Y., Zhang, J., Chen, M., Ma, M., and Sheng, B. (2022). Elevated serum triglyceride levels may be a key independent predicting factor for gallbladder cancer risk in gallbladder stone disease patients: A case\u2013control study. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-01189-y"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/jgh.16477","article-title":"Metabolic syndrome, its components, and gastrointestinal cancer risk: A meta-analysis of 31 prospective cohorts and Mendelian randomization study","volume":"39","author":"Zhan","year":"2024","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Borena, W., Edlinger, M., Bj\u00f8rge, T., H\u00e4ggstr\u00f6m, C., Lindkvist, B., Nagel, G., Engeland, A., Stocks, T., Strohmaier, S., and Manjer, J. (2014). A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089368"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.7150\/jca.54617","article-title":"Effect of metabolic syndrome components on the risk of malignancy in patients with gallbladder lesions","volume":"12","author":"Deng","year":"2021","journal-title":"J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/dmrr.2671","article-title":"Type 2 diabetes mellitus and risk of gallbladder cancer: A systematic review and meta-analysis of observational studies","volume":"32","author":"Gu","year":"2016","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_63","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_64","doi-asserted-by":"crossref","unstructured":"Jing, C., Wang, Z., and Fu, X. (2020). Effect of diabetes mellitus on survival in patients with gallbladder Cancer: A systematic review and meta-analysis. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07139-y"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wongjarupong, N., Assavapongpaiboon, B., Susantitaphong, P., Cheungpasitporn, W., Treeprasertsuk, S., Rerknimitr, R., and Chaiteerakij, R. (2017). Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: A systematic review and meta-analysis. BMC Gastroenterol., 17.","DOI":"10.1186\/s12876-017-0696-4"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sanna, C., Rosso, C., Marietti, M., and Bugianesi, E. (2016). Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050717"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1053\/j.gastro.2020.02.020","article-title":"Metabolic Inflammation\u2014A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease?","volume":"158","author":"Gehrke","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/cas.14828","article-title":"NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice","volume":"112","author":"Maeda","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nrgastro.2017.72","article-title":"The gut microbiome and liver cancer: Mechanisms and clinical translation","volume":"14","author":"Yu","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2016.85","article-title":"The role of the gut microbiota in NAFLD","volume":"13","author":"Leung","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Saab, M., Mestivier, D., Sohrabi, M., Rodriguez, C., Khonsari, M.R., Faraji, A., and Sobhani, I. (2021). Characterization of biliary microbiota dysbiosis in extrahepatic cholangiocarcinoma. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247798"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cld.2015.10.001","article-title":"Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the United States and the Rest of the World","volume":"20","author":"Sayiner","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/s00535-016-1264-3","article-title":"Nonalcoholic fatty liver disease in Asia: Emerging perspectives","volume":"52","author":"Seto","year":"2017","journal-title":"J. Gastroenterol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejca.2021.03.024","article-title":"Association between non-alcoholic fatty liver disease and the risk of biliary tract cancers: A South Korean nationwide cohort study","volume":"150","author":"Hong","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/MEG.0000000000001684","article-title":"Nonalcoholic fatty liver disease is associated with intrahepatic cholangiocarcinoma and not with extrahepatic form: Definitive evidence from meta-analysis and trial sequential analysis","volume":"33","author":"Corrao","year":"2020","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Takahashi, Y., Dungubat, E., Kusano, H., and Fukusato, T. (2023). Pathology and Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatic Tumors. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102761"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"E13","DOI":"10.1097\/HEP.0000000000000706","article-title":"From NAFLD to MASLD: Promise and pitfalls of a new definition\u2020","volume":"79","author":"Cusi","year":"2024","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"359","DOI":"10.5858\/arpa.2022-0537-RA","article-title":"Cholangiocarcinoma: Pathologic and Molecular Classification in the Era of Precision Medicine","volume":"148","author":"Gopal","year":"2024","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"154955","DOI":"10.1016\/j.metabol.2021.154955","article-title":"Metabolic dysfunction\u2013associated fatty liver disease and the risk of 24 specific cancers","volume":"127","author":"Liu","year":"2022","journal-title":"Metabolism"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s11605-013-2149-x","article-title":"Prevalence of nonalcoholic steatohepatitis among patients with resectable intrahepatic cholangiocarcinoma","volume":"17","author":"Reddy","year":"2013","journal-title":"J. Gastrointest. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/MEG.0b013e328357cdd7","article-title":"Peripheral intrahepatic cholangiocarcinoma occurring in patients without cirrhosis or chronic bile duct diseases: Epidemiology and histopathology of distant nontumoral liver in 57 White patients","volume":"25","author":"Nkontchou","year":"2013","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/ijc.22283","article-title":"Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: A nationwide case-control study","volume":"120","author":"Welzel","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/jso.24223","article-title":"The association between non-alcoholic steatohepatitis and intrahepatic cholangiocarcinoma: A hospital based case-control study","volume":"113","author":"Kinoshita","year":"2016","journal-title":"J. Surg. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/CEJ.0000000000000260","article-title":"Reproductive factors and gallbladder\/bile duct cancer: A population-based cohort study in Japan","volume":"26","author":"Makiuchi","year":"2017","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jhep.2020.04.046","article-title":"Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project","volume":"73","author":"Jackson","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.mehy.2007.06.040","article-title":"Cholesterol gallstones and cancer of gallbladder (CAGB): Molecular links","volume":"70","author":"Venniyoor","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/hep.1840060405","article-title":"Estrogen and progesterone receptors in human gallbladder","volume":"6","author":"Singletary","year":"1986","journal-title":"Hepatology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/sj.bjc.6605597","article-title":"Reproductive factors and risks of biliary tract cancers and stones: A population-based study in Shanghai, China","volume":"102","author":"Andreotti","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/ijc.34916","article-title":"Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium","volume":"155","author":"Shin","year":"2024","journal-title":"Int. J. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/GME.0000000000001019","article-title":"Age at natural menopause in Koreans: Secular trends and influences thereon","volume":"25","author":"Park","year":"2018","journal-title":"Menopause"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/GME.0000000000001307","article-title":"Secular trends and associated factors of age at natural menopause in Taiwanese women","volume":"26","author":"Shen","year":"2019","journal-title":"Menopause"},{"key":"ref_92","first-page":"2923","article-title":"Estrogen receptors in human gastric, hepatocellular, and gallbladder car-cinomas and normal liver tissues","volume":"15","author":"Ohnami","year":"1988","journal-title":"Gan Kagaku Ryoho."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/BF02471584","article-title":"Estrogen and progesterone receptors in gallbladder cancer","volume":"19","author":"Nakamura","year":"1989","journal-title":"Jpn. J. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s12664-009-0046-8","article-title":"Hormones and gallbladder cancer in women","volume":"28","author":"Barreto","year":"2009","journal-title":"Indian J. Gastroenterol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s12029-015-9698-z","article-title":"Female sex hormone receptors in gallbladder cancer","volume":"46","author":"Bharathi","year":"2015","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Hryciuk, B., P\u0119ksa, R., Bie\u0144kowski, M., Szymanowski, B., Radecka, B., Winnik, K., \u017bok, J., Cichowska, N., Iliszko, M., and Duchnowska, R. (2020). Expression of Female Sex Hormone Receptors, Connective Tissue Growth Factor and HER2 in Gallbladder Cancer. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-58777-y"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1200\/JCO.2017.75.3780","article-title":"Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results from MyPathway, an Open-Label, Phase IIa Multiple Basket Study","volume":"36","author":"Hainsworth","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1200\/JCO.2018.77.9777","article-title":"Ado-Trastuzumab Emtansine for Patients with HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial","volume":"36","author":"Li","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nature25475","article-title":"HER kinase inhibition in patients with HER2- and HER3-mutant cancers","volume":"554","author":"Hyman","year":"2018","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4291\/wjgp.v1.i2.50","article-title":"Role of sex hormones in the modulation of cholangiocyte function","volume":"1","author":"Mancinelli","year":"2010","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.3748\/wjg.v12.i22.3537","article-title":"Estrogens and the pathophysiology of the biliary tree","volume":"12","author":"Alvaro","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.3109\/0284186X.2015.1016627","article-title":"Reproductive factors and risk of biliary tract cancer in a population-based study","volume":"54","author":"Kilander","year":"2015","journal-title":"Acta Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"9093","DOI":"10.2147\/OTT.S226261","article-title":"Diosgenin Suppresses Cholangiocarcinoma Cells Via Inducing Cell Cycle Arrest and Mitochondria-Mediated Apoptosis","volume":"12","author":"Mao","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00432-012-1207-1","article-title":"Estrogen is increased in male cholangiocarcinoma patients\u2019 serum and stimulates invasion in cholangiocarcinoma cell lines in vitro","volume":"138","author":"Hunsawong","year":"2012","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3961\/jpmph.16.021","article-title":"Metabolic Risk Profile and Cancer in Korean Men and Women","volume":"49","author":"Ko","year":"2016","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_106","first-page":"20","article-title":"Stili di vita, fattori di rischio e prevenzione delle malattie oncologiche: Il ruolo del cardiologo [Lifestyle, risk factors and prevention of cancer: Role of the cardiologist]","volume":"20","author":"Ambrignani","year":"2019","journal-title":"G Ital. Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1046\/j.1365-2796.2000.00742.x","article-title":"Infections as a major preventable cause of human cancer","volume":"248","author":"Kuper","year":"2000","journal-title":"J. Intern. Med."},{"key":"ref_108","first-page":"400","article-title":"Chronic inflammation and cancer: The role of the mitochondria","volume":"25","author":"Kamp","year":"2011","journal-title":"Oncology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/annonc\/mdu042","article-title":"Body mass index and survival in women with breast cancer\u2014Systematic literature review and meta-analysis of 82 follow-up studies","volume":"25","author":"Chan","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/jnci\/djs207","article-title":"Physical activity, biomarkers, and disease outcomes in cancer survivors: A systematic review","volume":"104","author":"Friedenreich","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"16626","DOI":"10.1002\/cam4.6266","article-title":"Pre-diagnosis lipid levels and mortality after obesity-related cancer diagnosis in the Women\u2019s Health Initiative cardiovascular disease biomarker cohort","volume":"12","author":"Hovsepyan","year":"2023","journal-title":"Cancer Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1152\/physrev.00030.2014","article-title":"Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality","volume":"95","author":"Gallagher","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1677\/jme.1.02033","article-title":"Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes","volume":"36","author":"Kang","year":"2006","journal-title":"J. Mol. Endocrinol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jamaoncol.2015.6396","article-title":"Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer","volume":"2","author":"Cao","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.jacc.2016.05.083","article-title":"Aspirin and Cancer","volume":"68","author":"Patrignani","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/hep.31879","article-title":"Postdiagnosis Aspirin Use Associated With Decreased Biliary Tract Cancer\u2013Specific Mortality in a Large Nationwide Cohort","volume":"74","author":"Liao","year":"2021","journal-title":"Hepatology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/oncolo\/oyad063","article-title":"Survival Analysis of 1140 Patients with Biliary Cancer and Benefit from Concurrent Renin-Angiotensin Antagonists, Statins, or Aspirin with Systemic Therapy","volume":"28","author":"Gunchick","year":"2023","journal-title":"Oncologist"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/ajh.27106","article-title":"Long-term risk of venous thromboembolism among patients with gastrointestinal non-neoplastic and neoplastic diseases: A prospective cohort study of 484 211 individuals","volume":"99","author":"Yuan","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"bcr2014203941","DOI":"10.1136\/bcr-2014-203941","article-title":"Successful multidisciplinary treatment of hilar cholangiocarcinoma in a patient with complicated new-onset coronary artery disease","volume":"2014","author":"Fujikawa","year":"2014","journal-title":"BMJ Case Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5009\/gnl220477","article-title":"Clinical Significance of Venous Thromboembolism in Patients with Advanced Cholangiocarcinoma","volume":"18","author":"Kim","year":"2024","journal-title":"Gut Liver"},{"key":"ref_121","first-page":"444","article-title":"Venous thromboembolism in patients with cholangiocarcinoma: Focus on risk factors and impact on survival","volume":"24","author":"Jeon","year":"2012","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1007\/s00432-021-03794-1","article-title":"Predictors for thromboembolism in patients with cholangiocarcinoma","volume":"148","author":"Pfrepper","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1016\/j.jstrokecerebrovasdis.2013.12.031","article-title":"Multiple ischemic strokes caused by nonbacterial thrombotic endocarditis because of gallbladder cancer: A case report","volume":"23","author":"Yamane","year":"2014","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1007\/s11606-019-05166-5","article-title":"Nonbacterial Thrombotic Endocarditis Due to Primary Gallbladder Malignancy with Recurrent Stroke Despite Anticoagulation: Case Report and Literature Review","volume":"34","author":"Shoji","year":"2019","journal-title":"J. Gen. Intern. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1002\/cam4.5104","article-title":"Competing risk analysis of cardiovascular death in patients with primary gallbladder cancer","volume":"12","author":"Chen","year":"2023","journal-title":"Cancer Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Xia, Y., Lu, S., Huo, C., Fan, L., Lin, M., and Huang, J. (2023). Non cancer causes of death after gallbladder cancer diagnosis: A population-based analysis. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-40134-4"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1007\/BF02936968","article-title":"Cardiac metastasis from squamous cell carcinoma of gallbladder","volume":"32","author":"Suganuma","year":"1997","journal-title":"J. Gastroenterol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.3748\/wjg.v11.i13.2048","article-title":"Cardiac metastases of gallbladder carcinoma","volume":"11","author":"Inoue","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1161\/01.CIR.22.3.474","article-title":"Metastatic cancer to the heart. Review of the literature and report of 127 cases","volume":"22","author":"Hanfling","year":"1960","journal-title":"Circulation"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1136\/hrt.30.3.383","article-title":"Myocardial metastases. A pathological and electrocardiographic study","volume":"30","author":"Berge","year":"1968","journal-title":"Br. Heart J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.3748\/wjg.v28.i15.1508","article-title":"Novel approaches in search for biomarkers of cholangiocarcinoma","volume":"28","author":"Mocan","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"101970","DOI":"10.1016\/j.mcp.2024.101970","article-title":"Advances in omics-based biomarker discovery for biliary tract malignancy Diagnosis:A narrative review","volume":"76","author":"Xu","year":"2024","journal-title":"Mol. Cell. Probes"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.3892\/mmr.2014.2973","article-title":"Identification of bile biomarkers of biliary tract cancer through a liquid chromatography\/mass spectrometry-based metabolomic method","volume":"11","author":"Xu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1080\/02841850802220092","article-title":"Detection of cholangiocarcinoma with magnetic resonance spectroscopy of bile in patients with and without primary sclerosing cholangitis","volume":"49","author":"Albiin","year":"2008","journal-title":"Acta Radiol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Kishi, K., Kuwatani, M., Ohnishi, Y., Kumaki, Y., Kumeta, H., Hirata, H., Takishin, Y., Furukawa, R., Nagai, K., and Yonemura, H. (2023). Metabolomics of Duodenal Juice for Biliary Tract Cancer Diagnosis. Cancers, 15.","DOI":"10.3390\/cancers15174370"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yang, Z., Shi, Z., Zhu, Z., Li, C., Du, Z., Zhang, Y., Wang, Z., Jiao, Z., and Tian, X. (2021). Analysis of bile acid profile in plasma to differentiate cholangiocarcinoma from benign biliary diseases and healthy controls. J. Steroid Biochem. Mol. Biol., 205.","DOI":"10.1016\/j.jsbmb.2020.105775"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/hep.30852","article-title":"Characterization of Gut Microbiota, Bile Acid Metabolism, and Cytokines in Intrahepatic Cholangiocarcinoma","volume":"71","author":"Jia","year":"2020","journal-title":"Hepatology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1039\/C5MB00572H","article-title":"Serum metabolomics uncovering specific metabolite signatures of intra- and extrahepatic cholangiocarcinoma","volume":"12","author":"Liang","year":"2016","journal-title":"Mol. Biosyst."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/hep.30319","article-title":"Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis","volume":"70","author":"Banales","year":"2019","journal-title":"Hepatolongy"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jceh.2019.06.001","article-title":"Characterisation of the Serum Metabolic Signature of Cholangiocarcinoma in a United Kingdom Cohort","volume":"10","author":"Alsaleh","year":"2020","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00011-016-0998-y","article-title":"1H nuclear magnetic resonance (NMR)-based serum metabolomics of human gallbladder inflammation","volume":"66","author":"Sharma","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"63049","DOI":"10.1039\/C6RA09430A","article-title":"Urine metabolic phenotypes analysis of extrahepatic cholangiocarcinoma disease using ultra-high performance liquid chromatography-mass spectrometry","volume":"6","author":"Wang","year":"2016","journal-title":"RSC Adv."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"12365","DOI":"10.1007\/s00432-023-05119-w","article-title":"Identification and validation of a plasma metabolomics-based model for risk stratification of intrahepatic cholangiocarcinoma","volume":"149","author":"Tan","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1111\/jcmm.12868","article-title":"Potentials of single-cell biology in identification and validation of disease biomarkers","volume":"20","author":"Niu","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Chen, W., Xu, D., Liu, Q., Wu, Y., Wang, Y., and Yang, J. (2023). Unraveling the heterogeneity of cholangiocarcinoma and identifying biomarkers and therapeutic strategies with single-cell sequencing technology. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114697"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Golino, J.L., Wang, X., Maeng, H.M., and Xie, C. (2023). Revealing the Heterogeneity of the Tumor Ecosystem of Cholangiocarcinoma through Single-Cell Transcriptomics. Cells, 12.","DOI":"10.3390\/cells12060862"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jhep.2020.05.039","article-title":"Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma","volume":"73","author":"Zhang","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/s41467-022-29164-0","article-title":"Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma","volume":"13","author":"Song","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3558200","DOI":"10.1155\/2022\/3558200","article-title":"Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing","volume":"2022","author":"Bian","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.jhep.2022.05.043","article-title":"Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target","volume":"77","author":"Alvisi","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.jcmgh.2022.02.014","article-title":"Single-cell Transcriptomic Architecture Unraveling the Complexity of Tumor Heterogeneity in Distal Cholangiocarcinoma","volume":"13","author":"Li","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1186\/s12967-024-05238-z","article-title":"Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma","volume":"22","author":"Zhong","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.ccell.2021.03.012","article-title":"Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations","volume":"39","author":"Affo","year":"2021","journal-title":"Cancer Cell"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/19\/3432\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:09Z","timestamp":1760112609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/19\/3432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,9]]},"references-count":153,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["cancers16193432"],"URL":"https:\/\/doi.org\/10.3390\/cancers16193432","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2024,10,9]]}}}