Annals of Surgical Oncology

, Volume 13, Issue 7, pp 947–954 | Cite as

Specific Gene-Expression Profiles of Noncancerous Liver Tissue Predict the Risk for Multicentric Occurrence of Hepatocellular Carcinoma in Hepatitis C Virus–Positive Patients

  • Masahiro Okamoto
  • Tohru Utsunomiya
  • Shigeki Wakiyama
  • Masaji Hashimoto
  • Kengo Fukuzawa
  • Takahiro Ezaki
  • Taizo Hanai
  • Hiroshi Inoue
  • Masaki MoriEmail author



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.


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.


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).


Specific gene-expression signatures in noncancerous liver tissue may help to accurately predict the risk for developing HCC.


Hepatocellular carcinoma Multicentric occurrence Hepatitis C virus DNA microarray 



Supported by Grants-in-Aid for Scientific Research (17109013, 17591411, 17591413, 17015032, and 16390381), the Japan Society for the Promotion of Science, and a Health and Labor Sciences Research Grant on Hepatitis and BSE (14230801; the Ministry of Health, Labor and Welfare of Japan). Also supported by CREST, JST, Uehara Memorial Foundation, Yasuda Medical Research Foundation, Japanese Foundation for Multidisciplinary Treatment of Cancer, and Princess Takamatsu Cancer Research Fund.


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Copyright information

© The Society of Surgical Oncology, Inc. 2006

Authors and Affiliations

  • Masahiro Okamoto
    • 1
  • Tohru Utsunomiya
    • 1
  • Shigeki Wakiyama
    • 2
  • Masaji Hashimoto
    • 3
  • Kengo Fukuzawa
    • 4
  • Takahiro Ezaki
    • 5
  • Taizo Hanai
    • 6
  • Hiroshi Inoue
    • 1
  • Masaki Mori
    • 1
    Email author
  1. 1.Department of Molecular and Surgical OncologyMedical Institute of Bioregulation, Kyushu UniversityBeppuJapan
  2. 2.Department of SurgeryIizuka HospitalIizukaJapan
  3. 3.Department of Digestive SurgeryToranomon Hospital and Okinaka Memorial Institute for Medical ResearchTokyoJapan
  4. 4.Department of SurgeryOita Red Cross HospitalOitaJapan
  5. 5.Department of SurgeryHiroshima Red Cross Hospital and Atomic Bomb Survivors HospitalHiroshimaJapan
  6. 6.Laboratory for Bioinformatics, Graduate School of Systems Life SciencesKyushu UniversityFukuokaJapan

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