Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients.
OBJECTIVE
To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis.


METHODS
Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV) infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade F1-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed: normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios.


RESULTS
In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC.


CONCLUSIONS
We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.
Shao
Run-Xuan
RX
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo 113-8655, Japan.
Hoshida
Yujin
Y
Otsuka
Motoyuki
M
Kato
Naoya
N
Tateishi
Ryosuke
R
Teratani
Takuma
T
Shiina
Shuichiro
S
Taniguchi
Hiroyoshi
H
Moriyama
Masaru
M
Kawabe
Takao
T
Omata
Masao
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000502:physiology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction