title: Hepatic miR-126 is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma.
abstract: Controversies about the origin of circulating miRNAs have encouraged us to identify organ specific circulating miRNAs as disease biomarkers. To identify liver-specific miRNAs for hepatocellular carcinoma (HCC), global expression profiling of miRNAs in liver tissue of HBV-HCC and HBV-control with no or mild fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Among ten highly altered miRNAs, six miRNAs were successfully validated in tissues, whereas only two miRNAs, miR-126 and miR-142-3p showed increased expression in plasma of HBV-HCC compared to HBV-non-HCC patients. Subsequently, ROC curve analysis revealed that neither miR-126 nor miR-142-3p performed better than AFP in discriminating HCC from non-HCC while combination of each with AFP showed significantly higher efficiency rather than AFP alone (AUC: 0.922, 0.908 vs. 0.88; sensitivity: 0.84, 0.86 vs. 0.82 and specificity: 0.92, 0.94 vs. 0.86 respectively). Interestingly, triple combination of markers (miR-126 + miR-142-3p + AFP) showed no additive effect on efficiency (AUC: 0.925) over the dual combination. Again, the expression of only miR-126 was noticed significantly higher in HBV-HCC patients with low-AFP [<250 ng/ml] compared to either non-HCC or liver cirrhosis (AUC: 0.77, 0.64, respectively). Furthermore, no alteration in expression of mir-126 in HCV-HCC or non-viral-HCC revealed that miR-126 + AFP might be specific to HBV-HCC. To understand the physiological role of these two miRNAs in hepato-carcinogenesis, target genes related to cancer pathways (APAF1, APC2, CDKN2A, IRS1, CRKL, LIFR, EGR2) were verified. Thus, combination of circulating miR-126 + AFP is a promising noninvasive diagnostic biomarker for HBV-HCC and may be useful in the management of HCC patients.
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Alip
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Somenath
authors.initials: S
authors.lastname: Datta
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Debanjali
authors.initials: D
authors.lastname: Dasgupta
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Das
authors.affiliation: Division of Gastro-Intestinal Surgery, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Sukanta
authors.initials: S
authors.lastname: Ray
authors.affiliation: Centre for Liver and Biliary Surgery, Indraprastha Apollo Hospital, New Delhi, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Simanti
authors.initials: S
authors.lastname: Datta
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
authors.forename: Raghunath
authors.initials: R
authors.lastname: Chatterjee
authors.affiliation: National Institute of Biomedical Genomics, Kalyani, India.
authors.forename: Saroj Kant
authors.initials: SK
authors.lastname: Mohapatra
authors.affiliation: Department of Hepatology and School of Digestive and Liver Diseases, Centre for Liver Research, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Soma
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D019694:Hepatitis B, Chronic; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D000509:alpha-Fetoproteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D000509:alpha-Fetoproteins
keywords: HBV; HCC; MicroRNA; biomarker; hepatitis B virus; hepatocellular carcinoma; miR-126