MicroRNA profiling of hepatocarcinogenesis identifies C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma
Liver International, 04/13/2012
Augello C et al. – 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.
- 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.