title: Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini.
abstract: OBJECTIVE
  Intrahepatic cholangiocarcinoma (ICC) is a significant public health problem in East Asia, where it is strongly associated with chronic infection by the food-borne parasite Opisthorchis viverrini (OV). We report the first comprehensive miRNA expression profiling by microarray of the most common histologic grades and subtypes of ICC: well differentiated, moderately differentiated, and papillary ICC.
  
  
  METHODS
  MicroRNA expression profiles from FFPE were compared among the following: ICC tumour tissue (n = 16), non-tumour tissue distally macrodissected from the same ICC tumour block (n = 15), and normal tissue (n = 13) from individuals undergoing gastric bypass surgery. A panel of deregulated miRNAs was validated by qPCR.
  
  
  RESULTS
  Each histologic grade and subtype of ICC displayed a distinct miRNA profile, with no cohort of miRNAs emerging as commonly deregulated. Moderately differentiated ICC showed the greatest miRNA deregulation in quantity and magnitude, followed by the papillary subtype, and then well differentiated ICC. Moreover, when ICC tumour tissues were compared to adjacent non-tumour tissue, similar miRNA dysregulation profiles were observed.
  
  
  CONCLUSIONS
  We show that common histologic grades and subtypes of ICC have distinct miRNA profiles. As histological grade and subtypes are associated with ICC aggressiveness, these profiles could be used to enhance the early detection and improve the personalised treatment for ICC. These findings also suggest the involvement of specific miRNAs during ICC tumour progression and differentiation. We plan to use these insights to (a) detect these profiles in circulation and (b) conduct functional analyses to decipher the roles of miRNAs in ICC tumour differentiation.
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Plieskatt
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA; Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo 11800, Uruguay.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Infectious Disease and Cancer, Queensland Institute for Medical Research, Brisbane, Australia.
authors.forename: Ponlapat
authors.initials: P
authors.lastname: Yonglitthipagon
authors.affiliation: Department of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Easley
authors.affiliation: Department of Parasitology, Khon Kaen University School of Medicine, Khon Kaen 40002, Thailand.
authors.forename: Therawach
authors.initials: T
authors.lastname: Laha
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Vajarabhongsa
authors.initials: V
authors.lastname: Bhudhisawasdi
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: Infectious Disease and Cancer, Queensland Institute for Medical Research, Brisbane, Australia; School of Biomedical Sciences, Faculty of Medicine and Biomedical Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Mulvenna
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA; Research Center for the Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA. Electronic address: jbethony@gwu.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009889:Opisthorchiasis / Q000150:complications / Q000469:parasitology; D009891:Opisthorchis / Q000302:isolation & purification; D011379:Prognosis
chemical_list: D035683:MicroRNAs
keywords: Cholangiocarcinoma; Histological grade; Intrahepatic cholangiocarcinoma; MicroRNA; Microarray; Opisthorchis viverrini