title: A microRNA profile associated with Opisthorchis viverrini-induced cholangiocarcinoma in tissue and plasma.
abstract: BACKGROUND
  Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasite Opisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.
  
  
  METHODS
  We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.
  
  
  RESULTS
  Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically normal tissue adjacent to ICC tumor displayed miRNA expression profiles more similar to tumor than liver tissue from healthy donors. In plasma samples, an eight-miRNA signature associated with ICC, regardless of the degree of histological differentiation of its matched tissue, forming the basis of a circulating miRNA-based biomarker for ICC.
  
  
  CONCLUSIONS
  The association of unique miRNA profiles with different ICC subtypes suggests the involvement of specific miRNAs during ICC tumor progression. In plasma, an eight-miRNA signature associated with ICC could form the foundation of an accessible (plasma-based) miRNA-based biomarker for the early detection of ICC.
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. jordanp@gwu.edu.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. jordanp@gwu.edu.
authors.forename: Jordan
authors.initials: J
authors.lastname: Plieskatt
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. grinaldi@gwu.edu.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. grinaldi@gwu.edu.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. fengyanjun.fyj@gmail.com.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. fengyanjun.fyj@gmail.com.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. pj_2011@gwmail.gwu.edu.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. pj_2011@gwmail.gwu.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. seasley@mfa.gwu.edu.
authors.forename: Samantha
authors.initials: S
authors.lastname: Easley
authors.affiliation: QIMR Berghofer Medical Research Institute, Infectious Disease and Cancer, Brisbane, Queensland, 4006, Australia. sidney.jia@qimrberghofer.edu.au.
authors.forename: Xinying
authors.initials: X
authors.lastname: Jia
authors.affiliation: QIMR Berghofer Medical Research Institute, Infectious Disease and Cancer, Brisbane, Queensland, 4006, Australia. jeremy.potriquet@qimrberghofer.edu.au.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Potriquet
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. chawal-p@kku.ac.th.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. yoevajara@gmail.com.
authors.forename: Vajarabhongsa
authors.initials: V
authors.lastname: Bhudhisawasdi
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. banchob@kku.ac.th.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. pbrindley@email.gwu.edu.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. pbrindley@email.gwu.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. jbethony@gwu.edu.|Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, 20037, USA. jbethony@gwu.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bethony
authors.affiliation: QIMR Berghofer Medical Research Institute, Infectious Disease and Cancer, Brisbane, Queensland, 4006, Australia. jason.mulvenna@qimrberghofer.edu.au.|The University of Queensland, School of Biomedical Sciences, Brisbane, Queensland, 4072, Australia. jason.mulvenna@qimrberghofer.edu.au.
authors.forename: Jason
authors.initials: J
authors.lastname: Mulvenna
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood* / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D009891:Opisthorchis / Q000472:pathogenicity; D011379:Prognosis
chemical_list: D015415:Biomarkers; D035683:MicroRNAs