MicroRNA profiling of hepatocarcinogenesis identifies C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma

Liver International, 04/13/2012

C19MC cluster is a novel molecular alteration characteristic of liver cancer and predictor of poor prognosis. C19MC is an attractive candidate for novel hepatocellular carcinoma (HCC) therapies.

Methods

  • The authors used a low-density array platform to profile the expression of 664 mature miRNAin a cohort of 60 hepatitis Cvirus-positive liver lesions representative of all stages of progressive hepatocarcinogenesis.
  • They validated selected miRNA in two independent patient series by qPCRand they characterized the genomic status of the mi RNAcluster C19MCby fluorescent in situ hybridization and copy-number variation analyses.

Results

  • A 18-miRNA signature distinguished cirrhosis, dysplastic nodules and HCC lesions.
  • Four miRNAs overexpressed in HCCs belonged to chromosome 19 miRNA cluster (C19MC).
  • Significant overexpression of C19MC in early HCC compared to dysplastic nodules could be confirmed in a second series of hepatitis Bvirus-related liver lesions (n = 30).
  • In a third series of 61 HCCs, C19MCcluster was overexpressed in HCCs compared to matched cirrhotic parenchyma and regardless of the type of viral infection.
  • High C19MCmiRNAlevels were correlated with poor clinico-pathological features, increased risk of tumour recurrence and shorter overall survival time.
  • HCCs overexpressing the C19MCcluster showed genetic amplification of the corresponding locus.

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