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


METHODS
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.


CONCLUSIONS
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.
Jiang
Jinmai
J
College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Gusev
Yuriy
Y
Aderca
Ileana
I
Mettler
Teresa A
TA
Nagorney
David M
DM
Brackett
Daniel J
DJ
Roberts
Lewis R
LR
Schmittgen
Thomas D
TD
D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D018450:Disease Progression; D020869:Gene Expression Profiling; D006525:Hepatitis, Viral, Human / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D035683:MicroRNAs / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
D035683:MicroRNAs; D012333:RNA, Messenger