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Exploratory study of prognostic and therapeutic target moleculars in advanced prostate cancer

Research Project

Project/Area Number 21592029
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionAkita University

Principal Investigator

TSUCHIYA Norihiko  秋田大学, 大学院・医学系研究科, 准教授 (70282176)

Co-Investigator(Kenkyū-buntansha) HABUCHI Tomonori  秋田大学, 大学院・医学系研究科, 教授 (00293861)
HORIKAWA Yohei  秋田大学, 医学部, 講師 (40361232)
NARITA Shintaro  秋田大学, 医学部, 講師 (40396552)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords腫瘍学 / 前立腺癌 / 予後予測 / 遺伝子多型 / SNPアレイ / 治療標的分子 / SNPパネル / 予後診断 / IGF-I / IGF-I受容体 / 免疫染色
Research Abstract

Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. A total of 185 PCa patients with bone metastasis at initial diagnosis were analyzed. Each patient was genotyped using a Cancer SNP panel that contained 1421 SNPs in 408 cancer-related genes. SNPs associated with the survival were screened by log rank test. Fourteen SNPs in six genes, XRCC4, PMS1, GATA3, IL13, CASP8, and IGF1, were identified to have statistically significant association with the cancer-specific survival. The cancer-specific survivals of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 vs 2-3 vs 4-6 risk genotypes, P = 7.20 × 10-8). The high-risk group was independently associated with the survival in a multivariate analysis that included conventional clinicopathological variables (P=1.8x10-7). We identified 14 SNPs in 6 cancer-related genes which were associated with poor survival in patients with metastatic PCa. A panel of SNPs may help predict the survival of those patients.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010 2009 Other

All Journal Article (19 results) (of which Peer Reviewed: 11 results) Presentation (19 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Outcome, clinical prognostic factors and genetic predictors of adverse reactions of intermittent combination chemotherapy with docetaxel, estramustine phosphate and carboplatin for castration-resistant prostate cancer2011

    • Author(s)
      Narita S, Tsuchiya N, Yuasa T, et al
    • Journal Title

      Int J Clin Oncol

    • NAID

      10030951423

    • Related Report
      2011 Final Research Report
  • [Journal Article] Overexpression of Fn14 Promotes Androgen Independent Prostate Cancer Progression through MMP-9 and Correlates with Poor Treatment Outcome2011

    • Author(s)
      Huang M, Narita S, Tsuchiya N, et al
    • Journal Title

      Carcinogenesis

    • Related Report
      2011 Final Research Report
  • [Journal Article] 前立腺癌における遺伝子多型2011

    • Author(s)
      土谷順彦, 羽渕友則
    • Journal Title

      日本臨牀

      Volume: 69 Pages: 79-86

    • Related Report
      2011 Final Research Report
  • [Journal Article] 前立腺癌の発症・進展メカニズム2011

    • Author(s)
      井上高光, 土谷順彦, 羽渕友則
    • Journal Title

      日本臨牀

      Volume: 69 Pages: 79-86

    • Related Report
      2011 Final Research Report
  • [Journal Article] Outcome, clinical prognostic factors and genetic predictors of adverse reactions of intermittent combination chemotherapy with docetaxel, estramustine phosphate and carboplatin for castration-resistant prostatecancer2011

    • Author(s)
      Narita S, Tsuchiya N, Yuasa T, et al.
    • Journal Title

      Int J Clin Oncol

      Volume: (Epub) Issue: 3 Pages: 204-211

    • DOI

      10.1007/s10147-011-0275-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study2011

    • Author(s)
      Kote-Jarai Z, Olama AA, Giles GG, et al.
    • Journal Title

      Nat Genet

      Volume: 43 Issue: 8 Pages: 785-791

    • DOI

      10.1038/ng.882

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of Fn14 Promotes Androgen Independent Prostate Cancer Progression through MMP-9 and Correlates with Poor Treatment Outcome2011

    • Author(s)
      Huang M, Narita S, Tsuchiya N, et al.
    • Journal Title

      Carcinogenesis

      Volume: (Epub) Issue: 11 Pages: 1589-96

    • DOI

      10.1093/carcin/bgr182

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor2011

    • Author(s)
      Frullanti E, Berking C, Harbeck N, et al.
    • Journal Title

      Eur J Cancer Prev

      Volume: 20 Issue: 4 Pages: 340-347

    • DOI

      10.1097/cej.0b013e3283457274

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of polymorphism and expression of chromogranin a and endothelin-1 in prostate cancer2010

    • Author(s)
      Ma Z, Tsuchiya N, Yuasa T, et al
    • Journal Title

      J Urol

      Volume: 184 Pages: 1182-8

    • Related Report
      2011 Final Research Report
  • [Journal Article] 遺伝子多型による化学療法の副作用予測2010

    • Author(s)
      土谷順彦, 成田伸太郎, 井上高光, 他
    • Journal Title

      日本臨牀

      Volume: 68 Pages: 371-375

    • Related Report
      2011 Final Research Report
  • [Journal Article] Two survivin polymorphisms are cooperatively associated with bladder cancer susceptibility2010

    • Author(s)
      Kawata N
    • Journal Title

      Int J Cancer (Epub ahead of print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between bone mineral density and androgen-depr ivation therapy in Japanese prostate cancer patients2010

    • Author(s)
      Yuasa T
    • Journal Title

      Urology

      Volume: 75

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel tumor-suppressor Mel-18 in prostate cancer : its functional polymorphism, expression and clinical significance2009

    • Author(s)
      Wang W, Yuasa T, Tsuchiya N, et al
    • Journal Title

      Int J Cancer

      Volume: 125 Pages: 2836-43

    • Related Report
      2011 Final Research Report
  • [Journal Article] Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer2009

    • Author(s)
      Tsuchiya N, Narita S, Kumazawa T, et al
    • Journal Title

      Oncol Rep

      Volume: 22 Pages: 493-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer2009

    • Author(s)
      Tsuchiya N
    • Journal Title

      Oncol Rep 22

      Pages: 493-499

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravesical administration of gammadelta T cells successfully prevents the growth of bladder cancer in the murine model2009

    • Author(s)
      Yuasa T
    • Journal Title

      Cancer Immunol Immunother 58

      Pages: 493-502

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel tumor-suppressor Mel-18 in prostate cancer : Its functional polymorphism, expression, and clinical significance2009

    • Author(s)
      Wang W
    • Journal Title

      Int J Cancer 125

      Pages: 2836-843

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cystoprostatectomy as a treatment of prostate cancer involving the bladder neck2009

    • Author(s)
      Kumazawa T
    • Journal Title

      Urol Int 83

      Pages: 141-145

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of skeletal complications and their impact on survival of hormone refractory prostate cancer patients in Japan2009

    • Author(s)
      Inoue T
    • Journal Title

      Urology 73

      Pages: 1104-1109

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Prediction of survival in metastatic prostate cancer patients by single nucleotide polymorphisms of cancer-associated genes2012

    • Author(s)
      Yohei Horikawae, et al.
    • Organizer
      International EAUN Meeting
    • Place of Presentation
      Paris
    • Year and Date
      2012-02-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prediction of survival in metastatic prostate cancer patients by single nucleotide polymorphisms of cancer-associated genes2012

    • Author(s)
      Takamitsu Inoue, et al.
    • Organizer
      American Society of Clinical Oncology, Genitourinary Cancers Sypodium
    • Place of Presentation
      San Francisco
    • Year and Date
      2012-02-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prediction of Survival in Metastatic Prostate Cancer Patients by SNP Array Analysis of Cancer-Associated Genes2011

    • Author(s)
      Norihiko Tsuchiya, et al.
    • Organizer
      日本癌学会総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prediction of Survival in Metastatic Prostate Cancer Patients by SNP Array Analysis of Cancer-Associated Genes2011

    • Author(s)
      Norihiko Tsuchiya, et al.
    • Organizer
      American Urological Association Annual Meeting
    • Place of Presentation
      Washington DC
    • Year and Date
      2011-05-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] SNPアレイを用いた進行性前立腺癌の生存期間に関与する癌関連遺伝子の探索2011

    • Author(s)
      土谷順彦, 他
    • Organizer
      日本泌尿器科学会総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-04-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prostate cancer progression under high-fat diet is enhanced by MCP-1/CCR2 singaling2011

    • Author(s)
      Huang M, Narita S, Numakura K, et al
    • Organizer
      The 106th Annual Meeting of the American Urological Association Washington D.C.
    • Related Report
      2011 Final Research Report
  • [Presentation] Preoperative serum levels of interleukin-6 and interleukin-12 predict biochemical recurrence in patients with prostate cancer treated using radical prostatectomy2011

    • Author(s)
      Narita S, Tsuchiya N, Maita S, et al
    • Organizer
      The 106th Annual Meeting of the American Urological Association Washington D.C.
    • Related Report
      2011 Final Research Report
  • [Presentation] Prediction of Survival in Metastatic Prostate Cancer Patients by SNP Array Analysis of Cancer-Associated Genes2011

    • Author(s)
      Tsuchiya N, Matsui S, Narita S, et al
    • Organizer
      The 106th Annual Meeting of the American Urological Association Washington D.C.
    • Related Report
      2011 Final Research Report
  • [Presentation] Insulin-like growth factor-I (IGF-I) polymorphisms predict the survival of prostate cancer patients with bone metastasis at initial presentation2010

    • Author(s)
      Tsuchiya N
    • Organizer
      The 104th Annual Meeting of the American Urological Association
    • Place of Presentation
      San Francisco
    • Year and Date
      2010-06-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Tweak-Fn14 singnaling regulates androgen-independent prostate cancer cell invasiveness and correlates with poor patient outcome2010

    • Author(s)
      Huang M, Narita S, Ma Z, et al
    • Organizer
      The 105th Annual Meeting of the American Urological Association
    • Related Report
      2011 Final Research Report
  • [Presentation] Genetic polymorphism influences individual variations in serum testosterone levels in prostate cancer patients treated with androgen deprevation therapy2010

    • Author(s)
      Narita S, Numakura K, Obara T, et al
    • Organizer
      The 105th Annual Meeting of the American Urological Association
    • Related Report
      2011 Final Research Report
  • [Presentation] Insulin-like growth factor-I (IGF-I) polymorphisms predict the survival of prostate cancer patients with bone metastasis at initial presentation2010

    • Author(s)
      Tsuchiya N, Narita S, Ma Z, et al
    • Organizer
      The 105th Annual Meeting of the American Urological Association San Francisco
    • Place of Presentation
      USA
    • Related Report
      2011 Final Research Report
  • [Presentation] 前立腺癌におけるchromogranin Aならびにendothelin-1の臨床的意義2009

    • Author(s)
      馬智勇
    • Organizer
      日本泌尿器科学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-04-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 骨転移を有する前立腺癌の予後におけるhGH, IGF, IL-6ならびにその受容体遺伝子多型の関与2009

    • Author(s)
      土谷順彦
    • Organizer
      日本泌尿器科学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-04-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population (moderated poster)2009

    • Author(s)
      Ma Z, Tsuchiya N, Yuasa T, et al
    • Organizer
      The 104th Annual Meeting of the American Urological Association Chicago
    • Place of Presentation
      USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Influence of polymorphisms and expression of chromogranin A and endothelin-1 on the development and progression of prostate cancer (moderated poster)2009

    • Author(s)
      Ma Z, Tsuchiya N, Yuasa T, et al
    • Organizer
      The 104th Annual Meeting of the American Urological Association Chicago
    • Place of Presentation
      USA
    • Related Report
      2011 Final Research Report
  • [Presentation] A genetic polymorphism of tge osteoprotegerin gene is associated with an increased risk of advanced prostate cancer (moderated poster)2009

    • Author(s)
      Narita N, Yuasa T, Tsuchiya N, et al
    • Organizer
      The 104th Annual Meeting of the American Urological Association Chicago
    • Place of Presentation
      USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Evaluation of outcomes and genetic predictive factors for prognosis and toxicity in hormone-refractory prostate cancer patients following combination therapy with docetaxel, estramustine, and carboplatin (moderated poster)2009

    • Author(s)
      Narita S, Tsuruta H, Saito M, et al
    • Organizer
      The 104th Annual Meeting of the American Urological Association Chicago
    • Place of Presentation
      USA
    • Related Report
      2011 Final Research Report
  • [Presentation] The novel fumor-suppressor Mel-18 in prostate cnacer : its functional polymorphism, expression, and clinical significance (moderated poster)2009

    • Author(s)
      Wang W, Yuasa T, Tsuchiya N, et al
    • Organizer
      The 104th Annual Meeting of the American Urological Association Chicago
    • Place of Presentation
      USA
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.akita-u.ac.jp/~hinyoki/default.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.akita-u.ac.jp/~hinyoki/default.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.akita-u.ac.jp/~hinyoki/researcher/researchresults.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.akita-u.ac.jp/~hinyoki/researcher/researchresults.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 前立腺癌の予後の予測方法2011

    • Inventor(s)
      羽渕友則, 土谷順彦
    • Industrial Property Rights Holder
      秋田大学
    • Industrial Property Number
      2011-186698
    • Filing Date
      2011-08-30
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 前立腺癌の予後の予測方法2011

    • Inventor(s)
      羽渕友則、土谷順彦
    • Industrial Property Rights Holder
      秋田大学
    • Industrial Property Number
      2011-186698
    • Filing Date
      2011-08-30
    • Related Report
      2011 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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