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The research to establish the recurrence predicting system for hepatocellular carcinoma patients by use of genome-wide microarray database and to identify therapeutic molecular targets

Research Project

Project/Area Number 16390377
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyoto University

Principal Investigator

SATOH Seiji  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (00303834)

Co-Investigator(Kenkyū-buntansha) SHIMAHARA Yasuyuki  Kyoto University, Graduate School of Medicine, Assistant professor, 医学研究科, 助教授 (30196498)
IWAO Jkai  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (60263084)
KISHIMOTO Michimasa  Kyoto Institute of Technology, professor, 工芸学研究科, 教授 (00144436)
FUKUSHIMA Masanori  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (80107820)
松井 茂之  京都大学, 医学研究科, 助教授 (80305854)
HASEGAWA Suguru  Kyoto University, Graduate School of Medicine, Lecturer (10362500)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2004: ¥8,100,000 (Direct Cost: ¥8,100,000)
KeywordsHepatocellular carcinoma / β-atenin / cDNA microarray / TaqMan PCR / LOH / Recurrence / SIAH1 / PEG10 / 定量的RT-PCR
Research Abstract

Results 1
We observed a high frequency of LOH on chromosome 16, which correlated with vascular invasiveness of tumors. We performed deletion mapping of chromosome 16 and then identified SIAH1 and found a correlation between its suppressed expression and progression. It has been shown that SIAH1 functions in the phosphorylation-independent degradation of β-catenin and induces apoptosis and growth arrest. To examine if the effects of SIAH1 over-expression depend on the altered β-catenin signaling pathway, we transferred SIAH1 gene into hepatoma cells. SIAH1 significantly induced growth arrest and apoptosis, despite of accumulation of aberrant β-catenin. SIAH1 interacts with another target protein but β-catenin. Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein, which is known to be frequently over-expressed in HCC and to promote cell proliferation. SIAH1 induces apoptosis and growth arrest in hepatoma cells through different mechanisms.
Results 2
Through a genome-wide cDNA microarray of hepatocellular carcinomas(HCCs), we identified a number a number of genes associated with tumor progression. Thus, to analyze expression profiles more precisely and establish a predictive system of intrahepatic recurrence after surgery, we performed second screening of 47 HCCs by TaqMan PCR consisting of 120 genes. Then we divided 47 HCCs into two groups. 25 HCCs are for training and 22 HCCs are blinded sets for validation. We identified 27 genes that associated with intrahepatic recurrence within 1 year after curative resection. A predictive score, based on expression profiles of 15 of the genes, correctly predicted the recurrent status in 16 of 22 HCCs in the blinded sets. A positive predictive value was 75% and negative predictive value was 71.4%. Accumulation of such data will make it possible to define the nature of individual tumors, to provide clues for identifying new therapeutic targets, and ultimately to optimize treatment of each patient.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (7 results)

All 2007 2006 2005 2003

All Journal Article (7 results)

  • [Journal Article] SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation-dependent and independent mechanisms2007

    • Author(s)
      Yoshibayashi H
    • Journal Title

      Oncology Reports (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SIAH1 causes growth arrest and apoptosis in hepatoma cells through β-catenin degradation -dependent and -independent mechanisms2007

    • Author(s)
      Yoshibayashi H
    • Journal Title

      Oncology Reports (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells.2006

    • Author(s)
      Obama K et al.
    • Journal Title

      Clin Cancer Res. 12(1)

      Pages: 70-76

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma.2005

    • Author(s)
      Obama K et al.
    • Journal Title

      Hepatology 41(6)

      Pages: 1339-1348

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma.2005

    • Author(s)
      Obama K et al.
    • Journal Title

      Oncol Rep. 14(3)

      Pages: 701-706

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SIAH 1 inactivation correlates with tumor progression in hepatocellular carcinomas.2003

    • Author(s)
      Matsuo K
    • Journal Title

      Genes Chromosomes Cancer. 36(3)

      Pages: 283-291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of PEG10 in Human Hepatocellular Carcinogenesis through Interaction with SIAH1.2003

    • Author(s)
      Okabe H
    • Journal Title

      Cancer research. 63

      Pages: 3043-3048

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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