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MicroRNA profiling of hepatocarcinogenesis identifies C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma
Author(s) -
Augello Claudia,
Vaira Valentina,
Caruso Luca,
Destro Annarita,
Maggioni Marco,
Park Young Nyun,
Montorsi Marco,
Santambrogio Roberto,
Roncalli Massimo,
Bosari Silvano
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2012.02795.x
Subject(s) - hepatocellular carcinoma , biomarker , microrna , profiling (computer programming) , oncology , cluster (spacecraft) , medicine , cancer research , bioinformatics , biology , gene , computer science , genetics , programming language , operating system
Background and aims Progressive hepatocarcinogenesis is a stepwise process that drives liver transformation. However, the molecular mechanisms of early liver transformation are far from clear. A role for micro RNA s (mi RNA ) as diagnostic and prognostic factors in human tumours, including hepatocellular carcinoma ( HCC ), is promising. We aimed to identify novel mi RNA as biomarkers for differential diagnosis and predictors of disease progression. Methods We used a low‐density array platform to profile the expression of 664 mature mi RNA in a cohort of 60 hepatitis C virus‐positive liver lesions representative of all stages of progressive hepatocarcinogenesis. We validated selected mi RNA in two independent patient series by qPCR and we characterized the genomic status of the mi RNA cluster C 19 MC by fluorescent in situ hybridization and copy‐number variation analyses. Results A 18‐mi RNA signature distinguished cirrhosis, dysplastic nodules and HCC lesions. Four mi RNA s overexpressed in HCC s belonged to chromosome 19 mi RNA cluster ( C 19 MC ). Significant overexpression of C19 MC in early HCC compared to dysplastic nodules could be confirmed in a second series of hepatitis B virus‐related liver lesions ( n = 30). In a third series of 61 HCC s, C19 MC cluster was overexpressed in HCC s compared to matched cirrhotic parenchyma and regardless of the type of viral infection. High C 19 MC mi RNA levels were correlated with poor clinico‐pathological features, increased risk of tumour recurrence and shorter overall survival time. HCC s overexpressing the C 19 MC cluster showed genetic amplification of the corresponding locus. Conclusions C 19 MC cluster is a novel molecular alteration characteristic of liver cancer and predictor of poor prognosis. C 19 MC is an attractive candidate for novel HCC therapies.