title: Differential Protein Expression Marks the Transition From Infection WithOpisthorchis viverrinito Cholangiocarcinoma.
abstract: Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world because of infection by the liver flukeOpisthorchis viverrini(Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labeling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected but not cancerous)versuscancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue. We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA,i.e.proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared with proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer.
authors.affiliation: From the ‡Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|§Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|¶Department of Thai Traditional Medicine, Faculty of Natural Resources, Rajamangala University of Technology Isan, SakonNakhon Campus.
authors.forename: Jarinya
authors.initials: J
authors.lastname: Khoontawad
authors.affiliation: §Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|‖Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: **Department of Veterinary Technology, Faculty of Veterinary Technology, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Rucksak
authors.initials: R
authors.lastname: Rucksaken
authors.affiliation: §Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|‡‡Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Porntip
authors.initials: P
authors.lastname: Pinlaor
authors.affiliation: §Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|§§Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.affiliation: §Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|§§Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.affiliation: §Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|¶¶Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Ake
authors.initials: A
authors.lastname: Pugkhem
authors.affiliation: ‖‖The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.
authors.forename: Alun
authors.initials: A
authors.lastname: Jones
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20052.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20052.
authors.forename: Jordan
authors.initials: J
authors.lastname: Plieskatt
authors.affiliation: QIMR Berghofer Medical Research Institute, Infectious Disease Program, Brisbane 4006, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Potriquet
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20052.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20052.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Bethony
authors.affiliation: From the ‡Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.|§Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
authors.affiliation: QIMR Berghofer Medical Research Institute, Infectious Disease Program, Brisbane 4006, Australia; Jason.Mulvenna@qimrberghofer.edu.au.|The University of Queensland, School of Biomedical Sciences, Brisbane 4072, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Mulvenna
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000097:blood / Q000209:etiology* / Q000469:parasitology*; D006224:Cricetinae; D005260:Female; D005399:Fishes; D006801:Humans; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism*; D009889:Opisthorchiasis / Q000097:blood / Q000150:complications* / Q000469:parasitology*; D009891:Opisthorchis / Q000502:physiology*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins