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

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

Research output: Contribution to journalArticle

446 Scopus citations

Abstract

Purpose: MicroRNA (miRNA) is a newclass 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 comparedwith 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 G1-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.

Original languageEnglish (US)
Pages (from-to)419-427
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number2
DOIs
StatePublished - Jan 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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