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Development of diagnostic system of early hepatocellular carcinoma by methylation of multiple genes

Research Project

Project/Area Number 21390379
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OKA Masaaki  山口大学, 大学院・医学系研究科, 教授 (70144946)

Co-Investigator(Kenkyū-buntansha) IIZUKA Norio  山口大学, 医学部附属病院, 准教授 (80332807)
HAMAMOTO Yoshihiko  山口大学, 大学院・医学系研究科, 教授 (90198820)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords肝癌 / メチル化遺伝子 / セルフリーDNA / メチル化
Research Abstract

There are few blood tests for an efficient detection of hepatocellular carcinoma(HCC) associated with hepatitis C virus(HCV) infection. The abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, -fetoprotein(AFP) and prothrombin-induced vitamin K absence II(PIVKA-II), and various combinations to detect HCC were evaluated. An optimal hybrid detector, built using data for 2 methylated genes(SPINT2 and SRD5A2), AFP, and PIVKA-II, achieved the most satisfactory ability to detect HCC in the training cohort(n=164) and an independent validation cohort(n=258). In the validation cohort, accuracy, sensitivity, and specificity of the hybrid detector for detection of HCC were 81. 4%, 73. 2%, and 87. 7%, respectively. Notably, even when detecting HCC 2cm in diameter, the hybrid detector maintained markedly high abilities(84. 6% accuracy, 72. 2% sensitivity, 87. 7% specificity). These results show that the optimal hybrid blood detector can detect HCV-related HCC more accurately.

Report

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

    (39 results)

All 2011 2010 2009

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (23 results)

  • [Journal Article] Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers2011

    • Author(s)
      Iizuka N, Oka M, Sakaida I, Moribe T, Miura T, Kimura N, Tamatsukuri S, Ishitsuka H, Uchida K, Terai S, Yamashita S, Okita K, Sakata K, Karino Y, Toyota J, Ando E, Ide T, Sata M, Tsunedomi R, Tsutsui M, Iida M, Tokuhisa Y, Sakamoto K, Tamesa T, Fujita Y,
    • Journal Title

      Clin Chim Acta

      Volume: Vol.412 Pages: 152-158

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of 42 kDa Tubulin Alpha-6 Chain Fragment in Well-differentiated Hepatocellular Carcinoma Tissues from Patients Infected with Hepatitis C Virus2011

    • Author(s)
      Kuramitsu Y, Takashima M, Yokoyama Y, Iizuka N, Tamesa T, Akada JK, Wang Y, Toda T, Sakaida I, Okita K, Oka M, Nakamura K
    • Journal Title

      Anticancer Res. 2011 Anticancer Res

      Volume: Vol 31(10) Pages: 3331-3336

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of four isoforms of aldolase B down-regulated in hepatocellular carcinoma tissues by means of two-dimensional Western blotting2011

    • Author(s)
      Wang Y, Kuramitsu Y, Ueno T, Suzuki N, Yoshino S, Iizuka N, Zhang X, Oka M, Nakamura K
    • Journal Title

      In Vivo

      Volume: Vol 25(6) Pages: 881-886

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of 42 kDa Tubulin Alpha-6 Chain Fragment in Well-differentiated Hepatocellular Carcinoma Tissues from Patients Infected with Hepatitis C Virus2011

    • Author(s)
      Kuramitsu Y
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 3331-3336

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of four isoforms of aldolase B down-regulated in hepatocellular carcinoma tissues by means of two-dimensional Western blotting2011

    • Author(s)
      Wang Y
    • Journal Title

      In Vivo

      Volume: 25 Pages: 881-886

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers.2011

    • Author(s)
      Iizuka N
    • Journal Title

      Clin Chim Acta

      Volume: 412 Pages: 152-158

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma2010

    • Author(s)
      Tsunedomia R, Ogawa Y, Iizuka N, Sakamoto K, Tamesa T, Moribe T, Oka M
    • Journal Title

      Int J Oncol

      Volume: Vol.36 Pages: 205-212

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preoperative assessment of methylated cyclin D2 gene circulating in the blood for prediction of early intrahepatic recurrence of hepatocellular carcinoma after hepatectomy2010

    • Author(s)
      Tsutsui M, Iizuka N, Moribe T, Miura T, Kimura N, Tamatsukuri S, Ishitsuka H, Fujita Y, Hamamoto Y, Tsunedomi R, Iida M, Tokuhisa Y, Sakamoto K, Tamesa T, Sakaida I, Oka M
    • Journal Title

      Clin Chim Acta

      Volume: Vol.411 Pages: 516-520

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased serum cell-free DNA levels in relation to inflammation are predictive of distant metastasis of esophageal squamous cell carcinoma2010

    • Author(s)
      Tomochika S, Iizuka N, Watanabe Y, Tsutsui M, Takeda S, Yoshino S, Ichihara K, Oka M
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: Vol.1 Pages: 89-92

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preoperative assessment of methylated cyclin D2 gene circulating in the blood for prediction of early intrahepatic recurrence of hepatocellular carcinoma after hepatectomy.2010

    • Author(s)
      Tsutsui M
    • Journal Title

      Clin Chim Acta

      Volume: 411 Pages: 516-520

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased serum cell-free DVA levels in relation to inflammation are predictive of distant metastasis of esophageal squamous cell carcinoma.2010

    • Author(s)
      Tomochika S
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: 1 Pages: 89-92

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma.2010

    • Author(s)
      Tsunedomia R
    • Journal Title

      Int J Oncol 36

      Pages: 205-212

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and quantative detection of CpG-methylation status using TaqMan PCR combined with methl-binding-domain polypeptide2009

    • Author(s)
      Kimura N, Moribe T, Iizuka N, Miura T, Tamatsukiri S, Ishitsuka H, Hamamoto Y, Oka M
    • Journal Title

      Clin Biochem

      Volume: Vol.42 Pages: 1113-1122

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylation of multiple genes as molecular markers for diagnosis of a small, well-differentiated hepatocellular carcinoma2009

    • Author(s)
      Moribe T, Iizuka N, Miura M, Kimura N, Tamatsukuri S, Ishitsuka H, Hamamoto Y, Sakamoto S, Tamesa T, Oka M
    • Journal Title

      Int J Cancer

      Volume: Vol.125 Pages: 388-397

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and quantative detection of CpG-methylation status using TaqMan PCR combined with methl-binding-domain polypeptide.2009

    • Author(s)
      Kimura N
    • Journal Title

      Clin Biochem 42

      Pages: 1113-1122

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methylation of multiple genes as molecular markers for diagnosis of a small, well differentiated hepatocellular carcinoma.2009

    • Author(s)
      Moribe T
    • Journal Title

      Int J Cancer 125

      Pages: 388-397

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ABCB6遺伝子上流配列のDNAメチル化レベルは肝細胞癌の二年以内肝内再発と関連する2011

    • Author(s)
      恒富亮一、岡正朗、飯塚徳男、浜本義彦、他
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋・国際会議場
    • Year and Date
      2011-10-05
    • Related Report
      2011 Final Research Report
  • [Presentation] ABCB6遺伝子上流配列のDNAメチル化レベルは肝細胞癌の二年以内肝内再発と関連する2011

    • Author(s)
      恒富亮一
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      国際会議場・名古屋
    • Year and Date
      2011-10-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血清CIMPと肝細胞癌の予後2011

    • Author(s)
      飯塚徳男、岡正朗、浜本義彦、他
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋・国際会議場
    • Year and Date
      2011-10-04
    • Related Report
      2011 Final Research Report
  • [Presentation] CIMPと肝細胞癌の予後2011

    • Author(s)
      飯塚徳男
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      国際会議場・名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] ABCB6遺伝子を遺伝子マーカーとしたHCV関連肝細胞癌の予後予測2011

    • Author(s)
      恒富亮一、岡正朗、飯塚徳男、浜本義彦、他
    • Organizer
      第66回日本消化器外科学会総会
    • Place of Presentation
      名古屋・国際会議場
    • Year and Date
      2011-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝細胞癌における転写関連因子RDBPの発現とその意義2011

    • Author(s)
      飯田通久、岡正朗、飯塚徳男、他
    • Organizer
      第66回日本消化器外科学会総会
    • Place of Presentation
      名古屋・国際会議場
    • Year and Date
      2011-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] ABCB6遺伝子を遺伝子マーカーとしたHCV関連肝細胞癌の予後予測2011

    • Author(s)
      恒富亮一
    • Organizer
      第66回日本消化器外科学会総会
    • Place of Presentation
      国際会議場・名古屋
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝細胞癌における転写関連因子RDBPの発現とその意義2011

    • Author(s)
      飯田通久
    • Organizer
      第66回日本消化器外科学会総会
    • Place of Presentation
      国際会議場・名古屋
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 術前血中メチル化(SPINT2)遺伝子による肝切除後の早期肝内再発・全生存期間予測2011

    • Author(s)
      筒井理仁、岡正朗、飯塚徳男、他
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      誌上発表(東日本大震災のため)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝細胞癌におけるRDBPの発現とその機能2011

    • Author(s)
      飯田通久、岡正朗、飯塚徳男、他
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      誌上発表(東日本大震災のため)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 術前血中メチル化(SPINT2)遺伝子による肝切除後の早期肝内再発・全生存期間予測2011

    • Author(s)
      筒井理仁
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      (震災により誌上発表)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝細胞癌におけるRDBPの発現とその機能2011

    • Author(s)
      飯田通久
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      (震災により誌上発表)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] ABCB6遺伝子のmRNA発現レベルは肝細胞癌の一年以内肝内再発と相関する2010

    • Author(s)
      恒富亮一、岡正朗、飯塚徳男、浜本義彦、他
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪・国際会議場
    • Year and Date
      2010-09-22
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] HCV陽性肝細胞癌における転写関連因子RDBPの発現の検討2010

    • Author(s)
      飯田通久、岡正朗、飯塚徳男、浜本義彦、他
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪・国際会議場
    • Year and Date
      2010-09-22
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] HCV陽性肝細胞癌における転写関連因子RDBPの発現の検討2010

    • Author(s)
      飯田通久、岡正朗、飯塚徳男、浜本義彦、他
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋・国際会議場
    • Year and Date
      2010-04-08
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 術前血中メチル化cyclin D2(CCND2)遺伝子による肝切除後の早期肝内再発予測2010

    • Author(s)
      筒井理仁、岡正朗、飯塚徳男、他
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋・国際会議場
    • Year and Date
      2010-04-08
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] 肝癌患者における血中メチル化CCND2遺伝子の術前測定による早期肝内再発予測2009

    • Author(s)
      飯田通久
    • Organizer
      第20回日本消化器癌発生学会総会
    • Place of Presentation
      広島・オリエンタルホテル広島
    • Year and Date
      2009-11-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] BASP1とSRD5A2遺伝子のDNAメチル化異常に基づく早期肝細胞癌診断2009

    • Author(s)
      恒富亮一、岡正朗、飯塚徳男、浜本義彦、他
    • Organizer
      BASP1とSRD5A2遺伝子のDNAメチル化異常に基づく早期肝細胞癌診断第68回日本癌学会学術総会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2009-10-03
    • Related Report
      2011 Final Research Report
  • [Presentation] BASP1とSRD5A2遺伝子のDNAメチル化異常に基づく早期肝細胞癌診断2009

    • Author(s)
      恒富亮一
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] HCV陽性肝細胞癌における転写調節因子RDBPの発現意義2009

    • Author(s)
      飯塚徳男、岡正朗、浜本義彦、他
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2009-10-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝癌の独立した予後規定因子としての血清メチル化RASSFIA遺伝子2009

    • Author(s)
      飯塚徳男
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] HCV陽性肝細胞癌における転写調節因子RDBPの発現意義2009

    • Author(s)
      飯田通久、岡正朗、飯塚徳男、他
    • Organizer
      第64回日本消化器外科学会総会
    • Place of Presentation
      大阪・国際会議場
    • Year and Date
      2009-07-16
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] HCV陽性肝癌における血清cell-freeDNA上昇の意義:進展と炎症に関する検討2009

    • Author(s)
      飯田通久、岡正朗、飯塚徳男、他
    • Organizer
      第109回日本外科学会定期学術集会
    • Place of Presentation
      福岡・国際会議場
    • Year and Date
      2009-04-03
    • Related Report
      2011 Final Research Report 2009 Annual Research Report

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

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