title: Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma.
abstract: BACKGROUND
  MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC.
  
  
  RESULTS
  62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = -0.494, P = 0.00002), alanine aminotransferase (ALT) (r = -0.309, P = 0.007), aspartate aminotransferase (r = -0.495, P = 0.000007), bilirubin (r = -0.362, P = 0.002), international normalized ratio (r = -0.338, P = 0.034) and γ-glutamyltransferase (r = -0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dC(T) of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%.
  
  
  CONCLUSIONS
  The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.
authors: Department of Medicine I, University of Frankfurt/M., Frankfurt, Germany.
authors: Verena
authors: V
authors: Bihrer
authors: Oliver
authors: O
authors: Waidmann
authors: Mireen
authors: M
authors: Friedrich-Rust
authors: Nicole
authors: N
authors: Forestier
authors: Simone
authors: S
authors: Susser
authors: Jörg
authors: J
authors: Haupenthal
authors: Martin
authors: M
authors: Welker
authors: Ying
authors: Y
authors: Shi
authors: Jan
authors: J
authors: Peveling-Oberhag
authors: Andreas
authors: A
authors: Polta
authors: Michael
authors: M
authors: von Wagner
authors: Heinfried H
authors: HH
authors: Radeke
authors: Christoph
authors: C
authors: Sarrazin
authors: Jörg
authors: J
authors: Trojan
authors: Stefan
authors: S
authors: Zeuzem
authors: Bernd
authors: B
authors: Kronenberger
authors: Albrecht
authors: A
authors: Piiper
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000150:complications* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D009336:Necrosis; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012709:Serum Albumin; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin