title: Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: MiR-483-5p as a potential biomarker.
abstract: BACKGROUND
  MicroRNAs (miRNA) are abundant in the circulation and play a central role in diverse biologic processes; they may be useful for early diagnosis of hepatocellular carcinoma.
  
  
  METHODS
  We conducted a two-phase, case-control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiates hepatocellular carcinoma cases from controls. Taqman low-density arrays were used to examine genome-wide miRNA expression for the discovery set, and quantitative real-time PCR was used to validate candidate miRNAs for both discovery and validation sets.
  
  
  RESULTS
  Sixty-six miRNAs were found to be significantly overexpressed in plasma of hepatocellular carcinoma cases compared with controls after adjusting for false discovery rate (P < 0.05). A volcano plot indicated that seven miRNAs had greater than 2-fold case-control differences with P < 0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p, and miR-520b) detectable in all samples with varied expression levels were further validated in a validation set. MiR-483-5p was statistically significantly overexpressed in hepatocellular carcinoma cases compared with controls (3.20 vs. 0.82, P < 0.0001). Hepatocellular carcinoma risk factors and clinic-pathological characteristics did not influence miR-483-5p expression. The combination of plasma miR-483-5p level and hepatitis C virus status can significantly differentiate hepatocellular carcinoma cases from controls with an area under the curve of 0.908 (P < 0.0001). The sensitivity and specificity were, respectively, 75.5% and 89.8%.
  
  
  CONCLUSIONS
  These preliminary results suggest the importance of dysregulated circulating miR-483-5p as a potential hepatocellular carcinoma biomarker.
  
  
  CONCLUSIONS
  Confirmation of aberrant expression of miR-483-5p in a large prospective hepatocellular carcinoma study will provide support for its application to hepatocellular carcinoma detection.
authors.affiliation: Authors' Affiliations: Departments of Environmental Health Sciences and Biostatistics, Mailman School of Public Health; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center; and Departments of Medicine and Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Antai
authors.initials: A
authors.lastname: Wang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Irina
authors.initials: I
authors.lastname: Gurvich
authors.forename: Abby B
authors.initials: AB
authors.lastname: Siegel
authors.forename: Helen
authors.initials: H
authors.lastname: Remotti
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C548912:MIRN483 microRNA, human; D035683:MicroRNAs