title: Urinary microRNA-192 and microRNA-21 as potential indicators for liver fluke-associated cholangiocarcinoma risk group.
abstract: Opisthorchis viverrini infection induces chronic inflammation in the bile ducts, leading to periductal fibrosis (PDF), which possibly associates to cholangiocarcinoma (CCA). Patients with CCA have a poor prognosis, which is linked to asymptomatic disease and late diagnosis. Hence, detecting early stage CCA is essential. Secretory miRNAs have been promoted as biomarkers for pathological changes associated with parasitic infections, fibrosis and/or cancer. We aimed to determine levels of miR-192 and miR-21 in the urine of O. viverrini infected, periductal fibrosis (PDF) and CCA groups using qRT-PCR. We found that miR-192 was significantly higher in O. viverrini infected, PDF and also CCA groups (p<0.05) than in healthy controls. By utilizing the Receiver Operation Characteristics (ROC) analysis, miR-192 differentiated patients with opisthorchiasis (the area under the curve; AUC=0.766), PDF subjects (AUC=0.781) and CCA patients (AUC=0.682) from healthy controls. MiR-21 was significantly higher in PDF and CCA groups (p<0.05) than in healthy controls. MiR-21 discriminated PDF subjects (AUC=0.735) and CCA patients (AUC=0.682) from healthy controls. Combined levels of these two miRNAs revealed an increased AUC of 0.812 for separating opisthorchiasis, AUC of 0.815 in discriminating PDF subjects, and AUC of 0.849 in differentiating CCA from healthy controls. Odds ratios (OR) indicated high levels of miR-192/miR-21 as risk predictors for opisthorchiasis, PDF and CCA. Levels of these miRNAs declined significantly for patients following praziquantel treatment. In conclusion, urinary miR-192/miR-21 have potential as risk indicators for opisthorchiasis and PDF-associated CCA in the endemic region.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Runglawan
authors.initials: R
authors.lastname: Silakit
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Suyanee
authors.initials: S
authors.lastname: Thongchot
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Thidarut
authors.initials: T
authors.lastname: Boonmars
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Supinda
authors.initials: S
authors.lastname: Koonmee
authors.affiliation: Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Attapol
authors.initials: A
authors.lastname: Titapun
authors.affiliation: Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.affiliation: Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Chamadol
authors.affiliation: Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand. Electronic address: nisana@kku.ac.th.
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
mesh_terms: D000328:Adult; D000818:Animals; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000469:parasitology / Q000652:urine; D001652:Bile Ducts / Q000473:pathology; D015415:Biomarkers / Q000652:urine; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000469:parasitology / Q000652:urine; D005260:Female; D005355:Fibrosis; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D016017:Odds Ratio; D009889:Opisthorchiasis / Q000150:complications / Q000175:diagnosis* / Q000469:parasitology / Q000652:urine; D009891:Opisthorchis / Q000502:physiology*; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C546783:MIRN192 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
keywords: Cholangiocarcinoma; Opisthorchis viverrini; Periductal fibrosis; Risk indicator; Urinary microRNAs