title: Identification of ID2 associated with invasion of hepatitis C virus-related hepatocellular carcinoma by gene expression profile.
abstract: 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.
authors.affiliation: Department of Digestive Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Tsunedomi
authors.forename: Norio
authors.initials: N
authors.lastname: Iizuka
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yamada-Okabe
authors.forename: Takao
authors.initials: T
authors.lastname: Tamesa
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Okada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Motonari
authors.initials: M
authors.lastname: Takashima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Shunji
authors.initials: S
authors.lastname: Uchimura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: Mamoru
authors.initials: M
authors.lastname: Yamada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: 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
chemical_list: D051797:Inhibitor of Differentiation Protein 2