Prediction of prognosis of hepatocellular carcinoma with use of measurement of methylated CCND2 gene in the blood

• Project/Area Number: 21591749
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: IIZUKA Norio 山口大学, 医学部附属病院, 准教授 (80332807)
• Co-Investigator(Kenkyū-buntansha): TOKUHISA Yoshihiro 山口大学, 医学部附属病院, 医員 (30379961)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肝癌 / 腫瘍検査学 / 肝臓外科

Research Abstract

The purpose of this study is to develop a minimally invasive predictive system with use of methylated CCND2 gene in the serum responsible for outcome of patients with hepatocellular carcinoma(HCC).
(1) We determined several conditions for serum collection and DNA extraction.
(2) We established a quantitative methylation-specific PCR analysis for CCND2 gene in serum.
(3) We demonstrated that methylation levels of CCND2 gene in serum were associated with poor outcome of patents
We reported the relevant research in the form of 9 papers(total of IF=26. 6) and read 17 papers at academic meetings

Research Products

• [Journal Article] Up-regulation of 42 kDa Tubulin Alpha-6 Chain Fragment in Well-differentiated Hepatocellular Carcinoma Tissues from Patients Infected with Hepatitis C Virus (2011)
  • Author(s): Kuramitsu Y, Iizuka N, 他
  • Journal Title: Anticancer Res Volume: 31(10): 3331-6
  • Peer Reviewed
• [Journal Article] Differential expression of up-regulated cofilin-1 and down-regulated cofilin-2 characteristic of pancreatic cancer tissues (2011)
  • Author(s): Wang Y, Iizuka N, 他
  • Journal Title: Oncology Rep Volume: 26(6): 1595-9
  • 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, 他
  • Journal Title: Clinica Chimica Acta Volume: 412(1-2): 152-8
  • Peer Reviewed
• [Journal Article] Differential express ion of up-regulated cofilin-1 and down-regulated cofilin-2 characteristic of pancreatic cancer tissues (2011)
  • Author(s): Wang Y, Iizuka N, et al
  • Journal Title: Oncology Rep Volume: 26 Pages: 1595-1599
  • DOI: 10.3892/or.2011.1447
  • 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 Virus (2011)
  • Author(s): Kuramitsu Y, Iizuka N, et al
  • Journal Title: Anticancer Res Volume: 31 Pages: 3331-3336
  • Peer Reviewed
• [Journal Article] Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers (2011)
  • Author(s): Norio Iizuka, et al.
  • Journal Title: Clinica Chimica Acta Volume: 412 Pages: 152-158
  • Peer Reviewed
• [Journal Article] Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma (2010)
  • Author(s): Tsutsui M, Iizuka N, 他
  • Journal Title: Clinica Chimica Acta Volume: 411(7-8): 516-20
  • Peer Reviewed
• [Journal Article] The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma (2010)
  • Author(s): Tsunedomi R, Iizuka N, 他
  • Journal Title: International journal of oncology Volume: 36(1): 205-12
  • Peer Reviewed
• [Journal Article] The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma. (2010)
  • Author(s): Tsunedomi Ryouichi, et al.
  • Journal Title: International journal of oncology Volume: 36 Pages: 205-212
  • Peer Reviewed
• [Journal Article] Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma. (2010)
  • Author(s): Tsutsui Masahito, et al.
  • Journal Title: Clinica Chimica Acti 411 Pages: 516-520
  • Peer Reviewed
• [Journal Article] High serum levels of vascular endothelial growth factor after hepatectomy are associated with poor prognosis in hepatocellular carcinoma (2009)
  • Author(s): Tamesa T, Iizuka N, 他
  • Journal Title: Hepato-gastroenterology Volume: 56(93): 1122-6
  • Peer Reviewed
• [Journal Article] Integrin alpha2 mediates selective metastasis to the liver (2009)
  • Author(s): Yoshimura K, Iizuka N, 他
  • Journal Title: Cancer Research Volume: 69(8): 7320-8
  • Peer Reviewed
• [Journal Article] Rapid and quantitative detection of CpG-methylation status using TaqMan PCR combined with methyl-binding-domain polypeptide (2009)
  • Author(s): Kimura N, Iizuka N, 他
  • Journal Title: Clinical Biochemistry Volume: 42(10-11): 1113-22
  • 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, Iizuka N, 他
  • Journal Title: Int J Cancer Volume: 125(2): 388-97
  • Peer Reviewed
• [Journal Article] Methylation of multiple genes as molecular markers for diagnosis of a small, well-differentiated hepatocellular carcinoma. (2009)
  • Author(s): Moribe Toyoki, et al.
  • Journal Title: International Journal of Cancer 125 Pages: 388-397
  • Peer Reviewed
• [Journal Article] High serum levels of vascular endothelial growth factor after hepatectomy are associated with poor prognosis in hepatocellular carcinoma. (2009)
  • Author(s): Tamesa Takao, et al.
  • Journal Title: Hepato-gastroenterology 56 Pages: 1122-1126
  • Peer Reviewed
• [Journal Article] Integrin alpha2 mediates selective metastasis to the liver. (2009)
  • Author(s): Yoshimura Kiyoshi, et al.
  • Journal Title: Cancer Research 69 Pages: 7320-7328
  • Peer Reviewed
• [Journal Article] Rapid and quantitative detection of CpG-methylation status using TaqMan PCR combined with methyl-binding-domain polypeptide. (2009)
  • Author(s): Kimura Naoki, et al.
  • Journal Title: Clinical Biochemistry 42 Pages: 1113-1122
  • 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
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [Presentation] 血清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: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [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: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-07-14
• [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: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-07-14
• [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: 東京国際フォーラム(東京)
  • Year and Date: 2011-05-25
• [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: 東京国際フォーラム(東京)
  • Year and Date: 2011-05-25
• [Presentation] 血清Cell-freeDNAinteglityにより化学療法効果予測 (2011)
  • Author(s): 友近忍
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2011-05-25
• [Presentation] HCV陽性肝細胞癌におけるRDBPの発現とその意義 (2010)
  • Author(s): 飯田通久
  • Organizer: 第21回日本消化器癌発生学会総会
  • Place of Presentation: 長野、軽井沢プリンスホテル
  • Year and Date: 2010-11-18
• [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
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] インテグリンによるがん肝転移のメカニズム (2010)
  • Author(s): 吉村清
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2010-09-23
• [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
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] 肝細胞癌におけるID2発現のHDA阻害剤への影響 (2010)
  • Author(s): 恒富亮一
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 東京、東京ステーションコンファレンス,サピアタワー
  • Year and Date: 2010-06-30
• [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
  • Organizer: 第19回日本癌病態治療研究会
  • Place of Presentation: 東京、東京ステーションコンファレンス,サピアタワー
  • Year and Date: 2010-06-30
• [Presentation] 術前血清メチル化cyclin D2(CCND2)遺伝子の計測による肝切除後の早期肝内再発予測 (2010)
  • Author(s): 筒井理仁、飯塚徳男, 他
  • Organizer: 第110回日本外科学会学術総会
  • Place of Presentation: 日名古屋国際会議場、名古屋
  • Year and Date: 2010-04-08
• [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
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2010-04-08
• [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
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2010-04-08
• [Presentation] 術前血清メチル化cyclin D2(CCND2)遺伝子の計測による肝切除後の早期肝内再発予測 (2010)
  • Author(s): 筒井理仁, 他
  • Organizer: 第110回日本外科学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08