title: Serum microRNAs as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma.
abstract: The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC) > 0·70 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between PSC and CC. After the validation phase, miR-200c was found to be expressed differentially in PSC versus controls, whereas miR-483-5p and miR-194 showed deregulated expression in CC compared with controls. We also demonstrate a difference in the expression of miR-222 and miR-483-5p in CC versus PSC. Combination of these specific miRNAs further improved the specificity and accuracy of diagnosis. This study provides a basis for the use of miRNAs as biomarkers for the diagnosis of PSC and CC.
authors: Humanitas Clinical and Research Center, Rozzano, MI, Italy.|International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
authors: F
authors: F
authors: Bernuzzi
authors: Unit of Computational Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors: F
authors: F
authors: Marabita
authors: Humanitas Clinical and Research Center, Rozzano, MI, Italy.
authors: A
authors: A
authors: Lleo
authors: Humanitas Clinical and Research Center, Rozzano, MI, Italy.
authors: M
authors: M
authors: Carbone
authors: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Humanitas Clinical and Research Center, Milan, Italy.
authors: M
authors: M
authors: Mirolo
authors: Department of Gastroenterology, Università Politecnica Delle Marche, Ancona, Italy.
authors: M
authors: M
authors: Marzioni
authors: Research, Central Texas Veterans Health Care System, Scott and White Digestive Disease Research Center, Scott and White, Department of Medicine, Division of Gastroenterology, Texas A&M University Health Science Center, Temple, TX, USA.
authors: G
authors: G
authors: Alpini
authors: Division of Gastroenterology, Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors: D
authors: D
authors: Alvaro
authors: Medical Department, Rikshospitalet, Oslo, Norway.
authors: K M
authors: KM
authors: Boberg
authors: Department of Medical Biotechnologies and Translational Medicine, University of Milan, Humanitas Clinical and Research Center, Milan, Italy.
authors: M
authors: M
authors: Locati
authors: Liver Surgery Unit, Department of Surgery, University of Milan School of Medicine, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: G
authors: G
authors: Torzilli
authors: Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: L
authors: L
authors: Rimassa
authors: Internal Medicine, Department of Medical and Surgical Sciences DIMEC, Alma Mater Studiorum, University of Bologna, Italy.
authors: F
authors: F
authors: Piscaglia
authors: Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA.
authors: X-S
authors: XS
authors: He
authors: Division of Gastroenterology and Hepatology, University of California Davis, Davis, CA, USA.
authors: C L
authors: CL
authors: Bowlus
authors: Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA.
authors: G-X
authors: GX
authors: Yang
authors: Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA.
authors: M E
authors: ME
authors: Gershwin
authors: Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA.|International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
authors: P
authors: P
authors: Invernizzi
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C554846:MIRN194 microRNA, human; C533896:MIRN200 microRNA, human; C525710:MIR222, human; C548912:MIRN483 microRNA, human
keywords: biomarkers; cholangiocarcinoma; liver cancer; miRNAs; primary sclerosing cholangitis