Identification of ID2 associated with invasion of hepatitis C virus-related hepatocellular carcinoma by gene expression profile.
Portal vein invasion (PVI) is a hallmark of metastatic potential of hepatocellular carcinoma (HCC) and is frequently found at a stage of moderately differentiated HCC. To identify genes involved in PVI of HCC associated with hepatitis C virus (HCV), we performed a comprehensive analysis of 12,600 genes in 35 moderately differentiated HCV-related HCCs by DNA microarray. Our supervised learning method identified 35 genes involved in PVI. Among the 35 identified genes, we focused on the inhibitor of DNA binding 2 (ID2), because it encodes a liver-rich dominant-negative helix-loop-helix protein. The microarray results for ID2 were reproduced by quantitative real-time reverse transcription (QRT)-PCR and Western blot analyses. In an independent set of HCV-related HCCs (n=28) and HCV-unrelated HCCs (n=14), our QRT-PCR showed that decrease in ID2 mRNA levels were associated with PVI in HCV-related HCC but not HCV-unrelated HCC. In conclusion, our results strongly suggest that ID2 plays an important role in PVI process of HCV-related HCC.
Tsunedomi
Ryouichi
R
Department of Digestive Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Iizuka
Norio
N
Yamada-Okabe
Hisafumi
H
Tamesa
Takao
T
Okada
Toshimasa
T
Sakamoto
Kazuhiko
K
Takashima
Motonari
M
Hamaguchi
Takeshi
T
Miyamoto
Takanobu
T
Uchimura
Shunji
S
Hamamoto
Yoshihiko
Y
Yamada
Mamoru
M
Oka
Masaaki
M
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000150:complications / Q000235:genetics*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
D051797:Inhibitor of Differentiation Protein 2