title: miR-122 negatively correlates with liver fibrosis as detected by histology and FibroScan.
abstract: OBJECTIVE
  To investigate whether expression of selected miRNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.
  
  
  METHODS
  Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections (types B, C), 19 with autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology (alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNA isolation, expression levels of miR-21, miR-122, miR-214, miR-221, miR-222, and miR-224 were determined using TaqMan MicroRNA Assays applying miR-140 as the reference. Selection of miRNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of miRNAs was correlated with fibrosis stage and liver stiffness (LS) value measured by transient elastography, as well as with serum alanine aminotransferase (ALT) level.
  
  
  RESULTS
  The expression of individual miRNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of miR-122 in stage F4 was statistically significant (P < 0.04). When analyzing miRNA expression in relation to fibrosis, levels of miR-122 and miR-221 showed negative correlations with fibrosis stage, and miR-122 was found to correlate negatively and miR-224 positively with LS values (all P < 0.05). ALT levels displayed a positive correlation with miR-21 (P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between miR-122 and fibrosis stage and LS values (P < 0.05), and in the samples of chronic viral hepatitis, between miR-221 and fibrosis stage (P < 0.01), whereas miR-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases (P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values (P < 0.01) when etiology of fibrosis was not taken into account.
  
  
  CONCLUSIONS
  Reduced expression of miR-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Halász
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Horváth
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pár
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: Klára
authors.initials: K
authors.lastname: Werling
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Schaff
authors.affiliation: Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Lendvai
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015536:Down-Regulation; D054459:Elasticity Imaging Techniques; D005819:Genetic Markers; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D000410:Alanine Transaminase
keywords: Expression; FibroScan; Liver fibrosis; METAVIR; miR-122; microRNA