Molecular Mechanisms Linking Risk Factors to Cholangiocarcinoma Development

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Mar 25

PMID 35326593

Authors

Ludovica Ceci

Tianhao Zhou

Ilaria Lenci

Vik Meadows

Lindsey Kennedy

Ping Li

Burcin Ekser

Martina Milana

Wenjun Zhang

Chaodong Wu

Keisaku Sato

Sanjukta Chakraborty

Shannon S Glaser

Heather Francis

Gianfranco Alpini

Leonardo Baiocchi

Affiliations

Soon will be listed here.

Abstract

The poor prognosis of cholangiocarcinoma in humans is related to several factors, such as (i) the heterogeneity of the disease, (ii) the late onset of symptoms and (iii) the limited comprehension of the carcinogenic pathways determining neoplastic changes, which all limit the pursuit of appropriate treatment. Several risk factors have been recognized, including different infective, immune-mediated, and dysmorphogenic disorders of the biliary tree. In this review, we report the details of possible mechanisms that lead a specific premalignant pathological condition to become cholangiocarcinoma. For instance, during liver fluke infection, factors secreted from the worms may play a major role in pathogenesis. In primary sclerosing cholangitis, deregulation of histamine and bile-acid signaling may determine important changes in cellular pathways. The study of these molecular events may also shed some light on the pathogenesis of sporadic (unrelated to risk factors) forms of cholangiocarcinoma, which represent the majority (nearly 75%) of cases.

Citing Articles

Effectiveness of cholangioscopy guided biopsy versus ERCP guided brushings in diagnosing malignant biliary strictures.

Skenteris G, Singletary T, Grasso L, Self S, Schammel D, Schammel C Surg Endosc. 2024; 39(2):1140-1146.

PMID: 39702565 DOI: 10.1007/s00464-024-11422-5.

The crosstalk between cholangiocytes and hepatic stellate cells promotes the progression of epithelial-mesenchymal transition and periductal fibrosis during Clonorchis sinensis infection.

Yi J, Jeong J, Won J, Chung S, Pak J Parasit Vectors. 2024; 17(1):151.

PMID: 38519993 PMC: 10958959. DOI: 10.1186/s13071-024-06236-2.

Ubiquitin-conjugating enzyme E2C (UBE2C) is a prognostic indicator for cholangiocarcinoma.

Ong K, Lai H, Sun D, Chen T, Huang S, Tian Y Eur J Med Res. 2023; 28(1):593.

PMID: 38102624 PMC: 10724938. DOI: 10.1186/s40001-023-01575-9.

LAMC2 is a potential prognostic biomarker for cholangiocarcinoma.

Ong K, Hsieh Y, Lai H, Sun D, Chen T, Huang S Oncol Lett. 2023; 26(6):533.

PMID: 38020294 PMC: 10655064. DOI: 10.3892/ol.2023.14120.

Any Role for Microbiota in Cholangiocarcinoma? A Comprehensive Review.

Elvevi A, Laffusa A, Gallo C, Invernizzi P, Massironi S Cells. 2023; 12(3).

PMID: 36766711 PMC: 9913249. DOI: 10.3390/cells12030370.

References

Arechavaleta-Velasco F, Perez-Juarez C, Gerton G, Diaz-Cueto L . Progranulin and its biological effects in cancer. Med Oncol. 2017; 34(12):194. PMC: 5810362. DOI: 10.1007/s12032-017-1054-7. View

Mitra S, De A, Chowdhury A . Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol. 2020; 5:16. PMC: 7063528. DOI: 10.21037/tgh.2019.09.08. View

Makiuchi T, Sobue T, Kitamura T, Sawada N, Iwasaki M, Yamaji T . Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer. J Epidemiol. 2018; 29(5):180-186. PMC: 6445799. DOI: 10.2188/jea.JE20180011. View

Xu B, Broome U, Ericzon B, Sumitran-Holgersson S . High frequency of autoantibodies in patients with primary sclerosing cholangitis that bind biliary epithelial cells and induce expression of CD44 and production of interleukin 6. Gut. 2002; 51(1):120-7. PMC: 1773278. DOI: 10.1136/gut.51.1.120. View

Karlsen T, Folseraas T, Thorburn D, Vesterhus M . Primary sclerosing cholangitis - a comprehensive review. J Hepatol. 2017; 67(6):1298-1323. DOI: 10.1016/j.jhep.2017.07.022. View

Ishikawa Y, Mori T, Kato Y, Machinami R, Priest N, Kitagawa T . Systemic deposits of thorium in thorotrast patients with particular reference to sites of minor storage. Radiat Res. 1993; 135(2):244-8. View

Hussain S, Schwank J, Staib F, Wang X, Harris C . TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene. 2007; 26(15):2166-76. DOI: 10.1038/sj.onc.1210279. View

Mertz A, Nguyen N, Katsanos K, Kwok R . Primary sclerosing cholangitis and inflammatory bowel disease comorbidity: an update of the evidence. Ann Gastroenterol. 2019; 32(2):124-133. PMC: 6394256. DOI: 10.20524/aog.2019.0344. View

Chirshev E, Oberg K, Ioffe Y, Unternaehrer J . Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer. Clin Transl Med. 2019; 8(1):24. PMC: 6715759. DOI: 10.1186/s40169-019-0240-y. View

10.

Chapman R, Fevery J, Kalloo A, Nagorney D, Boberg K, Shneider B . Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010; 51(2):660-78. DOI: 10.1002/hep.23294. View

11.

Fava G, Marzioni M, Benedetti A, Glaser S, DeMorrow S, Francis H . Molecular pathology of biliary tract cancers. Cancer Lett. 2006; 250(2):155-67. DOI: 10.1016/j.canlet.2006.09.011. View

12.

Cuenco J, Wehnert N, Blyuss O, Kazarian A, Whitwell H, Menon U . Identification of a serum biomarker panel for the differential diagnosis of cholangiocarcinoma and primary sclerosing cholangitis. Oncotarget. 2018; 9(25):17430-17442. PMC: 5915126. DOI: 10.18632/oncotarget.24732. View

13.

Isomoto H, Kobayashi S, Werneburg N, Bronk S, Guicciardi M, Frank D . Interleukin 6 upregulates myeloid cell leukemia-1 expression through a STAT3 pathway in cholangiocarcinoma cells. Hepatology. 2005; 42(6):1329-38. DOI: 10.1002/hep.20966. View

14.

Erice O, Labiano I, Arbelaiz A, Santos-Laso A, Munoz-Garrido P, Jimenez-Aguero R . Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression. Biochim Biophys Acta Mol Basis Dis. 2017; 1864(4 Pt B):1335-1344. DOI: 10.1016/j.bbadis.2017.08.016. View

15.

Baiocchi L, Sato K, Ekser B, Kennedy L, Francis H, Ceci L . Cholangiocarcinoma: bridging the translational gap from preclinical to clinical development and implications for future therapy. Expert Opin Investig Drugs. 2020; 30(4):365-375. PMC: 8441992. DOI: 10.1080/13543784.2021.1854725. View

16.

Chen Y, Wang H, Zhu S, Lan X . miR-483-5p promotes esophageal cancer progression by targeting KCNQ1. Biochem Biophys Res Commun. 2020; 531(4):615-621. DOI: 10.1016/j.bbrc.2020.07.037. View

17.

Loeuillard E, Fischbach S, Gores G, Ilyas S . Animal models of cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis. 2018; 1865(5):982-992. PMC: 6177316. DOI: 10.1016/j.bbadis.2018.03.026. View

18.

Banales J, Marin J, Lamarca A, Rodrigues P, Khan S, Roberts L . Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020; 17(9):557-588. PMC: 7447603. DOI: 10.1038/s41575-020-0310-z. View

19.

Younossi Z, Koenig A, Abdelatif D, Fazel Y, Henry L, Wymer M . Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2015; 64(1):73-84. DOI: 10.1002/hep.28431. View

20.

Jing W, Jin G, Zhou X, Zhou Y, Zhang Y, Shao C . Diabetes mellitus and increased risk of cholangiocarcinoma: a meta-analysis. Eur J Cancer Prev. 2011; 21(1):24-31. DOI: 10.1097/CEJ.0b013e3283481d89. View