Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus.
OBJECTIVE
The purpose of this study was to elucidate the molecular basis of hepatocellular carcinoma (HCC) caused by genotype-C hepatitis B virus (HBV).


METHODS
We compared molecular profiles of 15 HCCs and five non-tumorous livers, all of which were associated with genotype-C HBV infection, using DNA microarray technology.


RESULTS
Our supervised learning identified 237 genes whose expression differed between HCCs and non-tumorous livers. This result was validated by a false discovery rate of 0%. Levels of expression of 35 and 202 genes were higher and lower, respectively, in HCCs than in non-tumorous livers. Among the 237 genes, we highlighted the top 35 upregulated and top 35 down regulated genes in tumor. Interestingly, when overlapping genes were excluded, 12 (e.g., NM23-H2, MCM7, PARP1, YWHAH, HSPB1, and MSH2) of the top 34 upregulated genes and five (e.g., MT1A and MT3) of the top 33 downregulated genes were c-myc-regulated genes. The microarray data for five randomly selected genes (MCM7, UBE2L3, PPIA, CXCL12, and ASS) were confirmed by quantitative real-time reverse transcription-polymerase chain reaction.


CONCLUSIONS
Our results indicate that many c-myc-regulated genes are involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV.
Iizuka
Norio
N
Department of Surgery II, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Tsunedomi
Ryouichi
R
Tamesa
Takao
T
Okada
Toshimasa
T
Sakamoto
Kazuhiko
K
Hamaguchi
Takashi
T
Yamada-Okabe
Hisafumi
H
Miyamoto
Takanobu
T
Uchimura
Shunji
S
Hamamoto
Yoshihiko
Y
Oka
Masaaki
M
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D015536:Down-Regulation; D016259:Genes, myc; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction