title: Upregulation of 14-3-3 eta in chronic liver fluke infection is a potential diagnostic marker of cholangiocarcinoma.
abstract: OBJECTIVE
  To discover protein markers in chronic/advanced opisthorchiasis for the early detection of Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA).
  
  
  METHODS
  Liver tissues derived from normal hamsters and those with chronic/advanced opisthorchiasis (n = 5 per group) were subjected to 2DE and LC-MS/MS. Candidate protein expression was confirmed in hamster models and human CCA tissue microarray (TMA) using immunohistochemistry and Western blot.
  
  
  RESULTS
  Proteomics analysis detected 14-3-3 eta only in infected hamsters, not in uninfected controls. Immunohistochemistry and Western blot analysis confirmed low expression of 14-3-3 eta in normal hamster livers and demonstrated increased expression through time in infected livers. This protein was also observed in parasite organs, especially during the chronic phase of opisthorchiasis. Moreover, increased expression of 14-3-3 eta, relative to normal hamster livers, was observed during the early stage of CCA induced by OV infection and administration of N-nitrosodimethylamine. Immunohistochemical analysis of human TMA revealed that 14-3-3 eta was highly expressed in CCA (84.23%, 187/222 cases) but was not found in hepatocellular carcinoma or healthy liver tissues.
  
  
  CONCLUSIONS
  14-3-3 eta protein has potential as a screening and early diagnostic marker for CCA.
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ornuma
authors.initials: O
authors.lastname: Haonon
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 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, Thailand.|Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 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, Thailand.|Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Yaovalux
authors.initials: Y
authors.lastname: Chamgramol
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Kitti
authors.initials: K
authors.lastname: Intuyod
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Sudarat
authors.initials: S
authors.lastname: Onsurathum
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.|Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
mesh_terms: D048948:14-3-3 Proteins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000469:parasitology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism* / Q000469:parasitology; D002908:Chronic Disease; D006801:Humans; D008297:Male; D008647:Mesocricetus; D009889:Opisthorchiasis / Q000378:metabolism* / Q000469:parasitology; D009891:Opisthorchis / Q000378:metabolism; D040901:Proteomics; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor
keywords: 14-3-3 eta; Cholangiocarcinoma; Chronic opisthorchiasis; Diagnostic marker; Early marker