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Construction of highly individualized dyagnostic sustem by expresson level of biomarker genes

Research Project

Project/Area Number 17390532
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionNiigata University

Principal Investigator

TAKAGI Ritsuo  Niigata University, Institute ofMedicine and Dentistry, Professor (20143795)

Co-Investigator(Kenkyū-buntansha) NAGATA Masaki  Niigata University, Institute ofMedicine and Dentistry, Assistant Professor (10242439)
FUJITA Hajime  Niigata University, Institute of Medicine and Dentistry, Assistant professor (60271805)
SHINGAKI Susumu  Niigata University, Institute ofMedicine and Dentistry, Associate Professor (30134943)
SAKU Takashi  Niigata University, Institute ofMedicine and Dentistry, Professor (40145264)
HOSHINA Hideyuki  Niigata University, Medical & Dental Hospital, Lecturer (30173587)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥15,270,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsIntegrin / Tetraspanin / Biomarker / Cervical lymph node metastasis / Distant metastasis / Outcome / Oral squamous ell carcinoma / 予後判定 / 頚部リンパ節転移 / 死の転帰 / 遺伝子発現量 / 舌癌
Research Abstract

【Aim】 Gene expression analysis of oral squamous cell carcinoma tissues were ferformed with Integrin family genes (ITG), Tetraspanin genes (TSPAN), Cycline and CDK genes as biomarkers of the malignancy of the cancer.
【Material and method】 Total RNA were extracted from whole oral squamous carcinoma tissues, and were subjected to reversetranscription synthesis for first strand cDNAs as templates for the Mowing real-time polymerase chain reaction (RTQ-PCR) process. Real time monitoring of RTQ-PCR were done with TaqMan promes specific for each subjected gems.
69 cases of tongue squamous cell carcinoma and 73 cases of gingival squamous cell carcinoma of upper and lower jaws were used as the subject of the gene expression analysis. Integrin family genes: ITGA1, ITGA2, ITGA3, ITGA5, ITGA6, ITGAv, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, and Tetraspanin family genes; CD9, CD81,CD82,CD63,CD151, and growth factor related gene: EGFR, and cyclins / thire inhibitors: CCND1, CCND2, CDK4, CDK2, Ki67, and prot … More ease genes; MMP-1, -2, -3, -4, -7, -8, -9, -10, -11, -12, -13, -14, NM23 were all subjected to analyses Expression levels of house keeping genes (GAPD, ACTB, 18sRNA), and epitherial cytoskeleton molecule gene (KRT5), and desmosomal components molecule genes (JUP, PXN) were also quantified and used for standarization of the expression level of subjected genes in the process of analyses. These gene expression ratios were subjected to the relation analyses with cervical lymph node metastasis, other clinical parameters and death outcome based on unifactorial and seriese of multifactorial statistical methods.
【Results】
(1)ITGB4/JUP, ITGB5/ACTB demonstrated significant relation with the distant organ metastasis and death outcome. On the other hand, ITGA3/KRT5, ITGA3/JUP showed relation to cervical lymph node metastasis without uncontrollable consequences.
(2)CD9/ACTB, CD9/CD82, and some CD9, MMP-1 gene expression ratios demonstrated significant relation to cervical lymph node metastasis and death outcome.
(3)CCND1 showed relation to poor prognosis including cervical lymphnode metasitasis and death outcome.
(4)NM23 and EGFR didn't exhibit any significance with poor clinical outcomes.
【Discussion】 There seemed to be two types of metastatic trait in oral squamous cell carcinomas, one was ivasive phenotype within local regional metastasis and another was lymphnode metastasis with agrresive phenotype to metastatize to distant organs. These biological characteristics were effectively assesed with the expression levels of ITGA3, ITGB4 and ITGB5. Less

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (5 results)

All 2008 2007

All Journal Article (5 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Diagnostic value of ITGA3, ITGB4 and ITGB5 expression levels for the clinical outcome of tongue squamous cell carcinoma2008

    • Author(s)
      Kurokawa, et. al.
    • Journal Title

      Cancer 112

      Pages: 1272-81

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Diagnostic value of ITGA3, ITGB4 and ITGB5 expression levels for the clinical outcome of tongue squamous cell carcinoma2008

    • Author(s)
      Kurokawa, A. Nagata, M., Kitamura, N., Noman, A. Ohnishi, M., Ohyama, T., Kobayashi, T., Shingaki, S., Takagi, R
    • Journal Title

      Cancer 112

      Pages: 1272-81

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The 2G allele of promoter region of Matrix metalloproteinase-1 as an es sential pre-condition for the early onset of oral squamous cell carcinoma2007

    • Author(s)
      Nisizawa, et. al.
    • Journal Title

      BioMed Central Cancer 7

      Pages: 187-187

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma2007

    • Author(s)
      Nishizawa, R., Nagata, M., Kitamura, N., Fujita, H., Hoshina, H., Noman, Arhab, Kubota, T., Itagaki, M., Shingaki, S., Ohnishi, M., Kurita, H., Katsura, K, Saito, C., Yoshie, H., Takagi, R
    • Journal Title

      BMC Cancer 7

      Pages: 187-187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma2007

    • Author(s)
      Nisizawa, et. al.
    • Journal Title

      BioMed Central Cancer 7

      Pages: 187-187

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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