title: Specific gene-expression profiles of noncancerous liver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection produces chronic hepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma (HCC). A molecular analysis of the damaged liver tissues infected with HCV may identify specific gene-expression profiles associated with a risk for liver carcinogenesis.
  
  
  METHODS
  Forty patients with HCV-positive HCC were classified into two groups: single nodular HCC group (n = 28) and multicentric HCC group (n = 12). Using a complementary DNA microarray, we compared the gene-expression patterns of the noncancerous liver tissue specimens between the two groups. We also identified the differentially expressed genes related to multicentric recurrence in the liver remnant. We then evaluated whether a specific gene-expression profile can accurately estimate the risk for multicentric hepatocarcinogenesis.
  
  
  RESULTS
  We selected the 230 differentially expressed genes in the multicentric HCC group. A hierarchical clustering analysis identified a cluster that might be closely associated with the multicentric occurrence of HCC. On the basis of the gene-expression profiling of the 36 genes commonly associated with both multicentric HCC and multicentric recurrence, we created a scoring system to estimate the risk for multicentric hepatocarcinogenesis. The prediction score of patients in the multicentric HCC group with multicentric recurrence (19.9 +/- 9.2) was significantly higher (P < .05) than that in the single nodular HCC group without multicentric recurrence (-1.8 +/- 12.7).
  
  
  CONCLUSIONS
  Specific gene-expression signatures in noncancerous liver tissue may help to accurately predict the risk for developing HCC.
authors.affiliation: Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu, 874-0838, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Shigeki
authors.initials: S
authors.lastname: Wakiyama
authors.forename: Masaji
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Kengo
authors.initials: K
authors.lastname: Fukuzawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ezaki
authors.forename: Taizo
authors.initials: T
authors.lastname: Hanai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins