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

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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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu, 874-0838, Japan

    Masahiro Okamoto MD, Tohru Utsunomiya MD, Hiroshi Inoue MD & Masaki Mori MD

  2. Department of Surgery, Iizuka Hospital, Iizuka, Japan

    Shigeki Wakiyama MD

  3. Department of Digestive Surgery, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan

    Masaji Hashimoto MD

  4. Department of Surgery, Oita Red Cross Hospital, Oita, Japan

    Kengo Fukuzawa MD

  5. Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan

    Takahiro Ezaki MD

  6. Laboratory for Bioinformatics, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan

    Taizo Hanai MD

Authors
  1. Masahiro Okamoto MD
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  2. Tohru Utsunomiya MD
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  3. Shigeki Wakiyama MD
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  4. Masaji Hashimoto MD
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  5. Kengo Fukuzawa MD
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  6. Takahiro Ezaki MD
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  7. Taizo Hanai MD
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  8. Hiroshi Inoue MD
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  9. Masaki Mori MD
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Corresponding author

Correspondence to Masaki Mori MD.

Additional information

M. Okamoto and T. Utsunomiya contributed equally to this study.

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Okamoto, M., Utsunomiya, T., Wakiyama, S. et al. Specific Gene-Expression Profiles of Noncancerous Liver Tissue Predict the Risk for Multicentric Occurrence of Hepatocellular Carcinoma in Hepatitis C Virus–Positive Patients. Ann Surg Oncol 13, 947–954 (2006). https://doi.org/10.1245/ASO.2006.07.018

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  • DOI: https://doi.org/10.1245/ASO.2006.07.018

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