title: Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma.
abstract: Diagnosis of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), particularly HCC independent of cirrhosis etiology, presents a great challenge because of a lack of biomarkers. Here we test the hypothesis that expression profiles of microRNAs (miRNAs) in serum can serve as biomarkers for diagnosis of HBV infection and HBV-positive HCC. We recruited 513 subjects (210 controls and 135 HBV-, 48 hepatitis C virus (HCV)-, and 120 HCC-affected individuals) and employed a strategy of initial screening by Solexa sequencing followed by validation with TaqMan probe-based quantitative reverse transcription-PCR assay. First, because of a close link between chronic hepatitis B and HCC, we compared miRNA expression profiles in HBV serum with that in control serum and successfully obtained 13 miRNAs that were differentially expressed in HBV serum. This 13-miRNA-based biomarker accurately discriminated not only HBV cases from controls and HCV cases, but also HBV-positive HCC cases from control and HBV cases. Second, we directly compared miRNA expressions in HCC serum with those in controls and identified 6 miRNAs that were significantly upregulated in HCC samples. Interestingly, 2 of these miRNAs, miR-375 and miR-92a, were also identified by our first approach as HBV specific. When we employed 3 of these miRNAs (miR-25, miR-375, and let-7f) as biomarkers, we could clearly separate HCC cases from controls, and miR-375 alone had an ROC of 0.96 (specificity: 96%; sensitivity: 100%) in HCC prediction. In conclusion, our study demonstrates for the first time that serum miRNA profiles can serve as novel and noninvasive biomarkers for HBV infection and HBV-positive HCC diagnosis.
authors.affiliation: Institute for Virology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Li
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Hu
authors.forename: Zhen-Xian
authors.initials: ZX
authors.lastname: Zhou
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Fen-Yong
authors.initials: FY
authors.lastname: Liu
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhang
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shen
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D006515:Hepatitis B virus / Q000254:growth & development; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; C543351:MIRN25 microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human