Literature DB >> 18223217

Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival.

Jinmai Jiang1, Yuriy Gusev, Ileana Aderca, Teresa A Mettler, David M Nagorney, Daniel J Brackett, Lewis R Roberts, Thomas D Schmittgen.   

Abstract

PURPOSE: MicroRNA (miRNA) is a new class of small, noncoding RNA. The purpose of this study was to determine if miRNAs are differentially expressed in hepatocellular carcinoma (HCC). EXPERIMENTAL
DESIGN: More than 200 precursor and mature miRNAs were profiled by real-time PCR in 43 and 28 pairs of HCC and adjacent benign liver, respectively, and in normal liver specimens.
RESULTS: Several miRNAs including miR-199a, miR-21, and miR-301 were differentially expressed in the tumor compared with adjacent benign liver. A large number of mature and precursor miRNAs were up-regulated in the adjacent benign liver specimens that were both cirrhotic and hepatitis-positive compared with the uninfected, noncirrhotic specimens (P < 0.01). Interestingly, all of the miRNAs in this comparison had increased expression and none were decreased. The expression of 95 randomly selected mRNAs was not significantly altered in the cirrhotic and hepatitis-positive specimens, suggesting a preferential increase in the transcription of miRNA. Comparing the miRNA expression in the HCC tumors with patient's survival time revealed two groups of patients; those with predominantly lower miRNA expression and poor survival and those with predominantly higher miRNA expression and good survival (P < 0.05). A set of 19 miRNAs significantly correlated with disease outcome. A number of biological processes including cell division, mitosis, and G(1)-S transition were predicted to be targets of the 19 miRNAs in this group.
CONCLUSION: We show that a global increase in the transcription of miRNA genes occurs in cirrhotic and hepatitis-positive livers and that miRNA expression may prognosticate disease outcome in HCC.

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Year:  2008        PMID: 18223217      PMCID: PMC2755230          DOI: 10.1158/1078-0432.CCR-07-0523

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN: 1078-0432            Impact factor:   12.531


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