title: Gene expression profiling of hepatitis B- and hepatitis C-related hepatocellular carcinoma using graphical Gaussian modeling.
abstract: OBJECTIVE
  Gene expression profiling of hepatocellular carcinoma (HCC) and background liver has been studied extensively; however, the relationship between the gene expression profiles of different lesions has not been assessed.
  
  
  METHODS
  We examined the expression profiles of 34 HCC specimens (17 hepatitis B virus [HBV]-related and 17 hepatitis C virus [HCV]-related) and 71 non-tumor liver specimens (36 chronic hepatitis B [CH-B] and 35 chronic hepatitis C [CH-C]) using an in-house cDNA microarray consisting of liver-predominant genes. Graphical Gaussian modeling (GGM) was applied to elucidate the interactions of gene clusters among the HCC and non-tumor lesions.
  
  
  RESULTS
  In CH-B-related HCC, the expression of vascular endothelial growth factor-family signaling and regulation of T cell differentiation, apoptosis, and survival, as well as development-related genes was up-regulated. In CH-C-related HCC, the expression of ectodermal development and cell proliferation, wnt receptor signaling, cell adhesion, and defense response genes was also up-regulated. Many of the metabolism-related genes were down-regulated in both CH-B- and CH-C-related HCC. GGM analysis of the HCC and non-tumor lesions revealed that DNA damage response genes were associated with AP1 signaling in non-tumor lesions, which mediates the expression of many genes in CH-B-related HCC. In contrast, signal transducer and activator of transcription 1 and phosphatase and tensin homolog were associated with early growth response protein 1 signaling in non-tumor lesions, which potentially promotes angiogenesis, fibrogenesis, and tumorigenesis in CH-C-related HCC.
  
  
  CONCLUSIONS
  Gene expression profiling of HCC and non-tumor lesions revealed the predisposing changes of gene expression in HCC. This approach has potential for the early diagnosis and possible prevention of HCC.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Takara-Machi 13-1, Kanazawa 920-8641, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Ueda
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Horimoto
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Aburatani
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sakai
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Takatori
authors.forename: Hajime
authors.initials: H
authors.lastname: Sunagozaka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002448:Cell Adhesion / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016011:Normal Distribution; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D051766:Early Growth Response Protein 1; D050794:STAT1 Transcription Factor; D042442:Vascular Endothelial Growth Factors