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Integrated Analysis of Prognostic Gene Expression Profiles from Hepatitis B Virus-Positive Hepatocellular Carcinoma and Adjacent Liver Tissue

  • Translational Research and Biomarkers
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Abstract

Background

The tissue environment in the region of hepatocellular carcinoma (HCC) influences both vascular invasion and recurrence. Thus, HCC patient prognosis depends on the characteristics not only of the tumor but also those of adjacent surrounding liver tissue.

Materials and Methods

Expression profiles of both tumor and adjacent liver tissue following curative resection were measured to discriminate 56 hepatitis B virus-positive HCC patients into subgroups based on survival risk. This approach was further tested in 40 patients.

Results

Expression profiles of both tumor and adjacent liver tissue successfully discriminated 56 training samples into 2 subgroups, those at low- or high-risk for survival and recurrence. However, the prognostic gene set selected for tumor tissue was quite different from that for adjacent tissues. This variation in prognostic genes resulted in a change in allocation of patients within each low- or high-risk group. Combination of survival subgroups from tumor and adjacent liver tissue significantly improved the prediction of prognostic outcome. This integrative approach was confirmed to be effective in a further 40 test patients. A clinicopathological study showed that survival subgroups divided by tumor and adjacent liver tissue gene expression were also statistically associated with UICC stage and extent of cell differentiation, respectively.

Conclusions

Variation in gene expression during the nontumor stage as well as the tumor stage may affect the prognosis of HCC patients, and integration of the gene expression profiles of HCC and adjacent liver tissue increases discriminatory effectiveness between patient groups, predicting clinical outcomes with enhanced statistical reliability.

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Acknowledgment

This work was supported by grants from the National Nuclear R & D program and Human Genome Project, the Korean Ministry of Science and Technology. M.H.C. was supported by a grant from National Research Foundation of Korea (NRF-2010-0000784).

Author information

Authors and Affiliations

  1. Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Bu-Yeo Kim PhD, Je-Geun Lee PhD, Seon Rang Woo PhD, In-Chul Park PhD,, Chul Ju Han MD, PhD, Sang-Bum Kim MD, PhD, Sook-Hyang Jeong MD, PhD, Dong Wook Choi MD, PhD & Kee-Ho Lee PhD

  2. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

    Kyung-Suk Suh MD, PhD

  3. Department of Pathology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Sun-Hoo Park MD, PhD

  4. Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Chul Ju Han MD, PhD

  5. Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    Sang-Bum Kim MD, PhD

  6. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

    Sook-Hyang Jeong MD, PhD

  7. Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea

    Young Il Yeom PhD & Suk-Jin Yang PhD

  8. Department of Internal Medicine, National Cancer Center, Goyang, Korea

    Chang-Min Kim MD, PhD

  9. Department of Pathology, Graduate School of Medicine, Korea University, Seoul, Korea

    Su Jin Cho PhD

  10. Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University, Seoul, Korea

    Young Do Yoo PhD

  11. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea

    Myung-Haing Cho PhD

  12. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

    Ja June Jang MD, PhD

  13. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Dong Wook Choi MD, PhD

Authors
  1. Bu-Yeo Kim PhD
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  2. Kyung-Suk Suh MD, PhD
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  12. Chang-Min Kim MD, PhD
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  17. Dong Wook Choi MD, PhD
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  18. Kee-Ho Lee PhD
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Corresponding authors

Correspondence to Dong Wook Choi MD, PhD or Kee-Ho Lee PhD.

Additional information

Bu-Yeo Kim and Kyung-Suk Suh contributed equally to this work.

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Kim, BY., Suh, KS., Lee, JG. et al. Integrated Analysis of Prognostic Gene Expression Profiles from Hepatitis B Virus-Positive Hepatocellular Carcinoma and Adjacent Liver Tissue. Ann Surg Oncol 19 (Suppl 3), 328–338 (2012). https://doi.org/10.1245/s10434-011-1709-0

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  • DOI: https://doi.org/10.1245/s10434-011-1709-0

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