Predictive blood system with use of methylation signatures for outcome of hepatocellular carcinoma

• Project/Area Number: 24592002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• 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)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 肝癌 / メチル化 / 血清DNA

Outline of Final Research Achievements

The purpose of this study is to develop a minimally invasive predictive blood test with use of methylation signature specific to hepatocellular carcinoma (HCC) for outcome of HCC.
Out of 20 methylation genes with CpG islands in the promoter and exon 1 regions, we identified 6 genes, such as CFTR, RASF1A, and BASP, linked to metastatic potentials of HCC. We found that 6-genes predictive scoring system had sensitivity and specificity of 56% and 68% in predicting outcome of HCC in the training set. The system worked well (sensitivity and specificity of more than 60%) in the test set. Moreover, we found that number of genes positive for methylation is critical to understanding of metastatic potentials of HCC. We reported the relevant results in the form of 9 papers (2 Anticancer Res., 4 Int J Oncol ., 1J Transl Med, 1 Oncol Rep, and 1 Frontiers in Pahrmacology) and read 3 papers at academic meetings. We obtained a patent linked to methodology for the system.

Research Products

• [Journal Article] Preoperative serum methylation signature as prognostic tool after curative hepatectomy in patients with hepatocellular carcinoma (2015)
  • Author(s): Kanekiyo S, Iizuka N, Tsunedomi R, Tokumitsu Y, Hashimoto N, Tokuhisa Y, Maeda Y, Iida M, Sakamoto K, Tamesa T, Fujita Y, Yoshino S, Hazama S, Hamamoto Y, Oka M.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 997-1007
  • Peer Reviewed
• [Journal Article] An accurate prognostic staging system for hepatocellular carcinoma patients after curative hepatectomy (2015)
  • Author(s): Y. Tokumitsu
  • Journal Title: International Journal of Oncology Volume: 46 Issue: 3 Pages: 944-952
  • DOI: 10.3892/ijo.2014.2798
  • Peer Reviewed / Open Access
• [Journal Article] Predictive biomarkers for the outcome of vaccination of five therapeutic epitope peptides for colorectal cancer. (2014)
  • Author(s): Hazama S, Takenouchi H, Tsunedomi R, Iida M, Suzuki N, Iizuka N, Inoue Y, Sakamoto K, Nakao M, Shindo Y, Kanekiyo S, Tokumitsu Y, Yoshimura K, Maeda N, Maeda K, Maeda Y, Matsui H, Yoshino S, Nakamura Y, Fujita Y, Hamamoto Y, Okamoto M, Fujita T, Kawakami Y, Oka M.
  • Journal Title: Anticancer Res. Volume: 34 Pages: 4201-4205
  • Peer Reviewed
• [Journal Article] A phase I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. (2014)
  • Author(s): Higashi K, Hazama S, Araki A, Yoshimura K, Iizuka N, Yoshino S, Noma T, Oka M.
  • Journal Title: Int J Oncol. Volume: 45 Issue: 4 Pages: 1412-1420
  • DOI: 10.3892/ijo.2014.2557
  • Peer Reviewed
• [Journal Article] Susceptibility of hepatoma-derived cells to histone deacetylase inhibitors is associated with ID2 expression. (2013)
  • Author(s): Tsunedomi R, Iizuka N. et al
  • Journal Title: Int J Oncol Volume: 42 Pages: 1159-1166
  • Peer Reviewed
• [Journal Article] ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma.
  • Author(s): Tsunedomi R, Iizuka N. et al
  • Journal Title: Int J Oncol Volume: 42 Pages: 1551-1559
  • Peer Reviewed
• [Presentation] 血清メチル化遺伝子による肝細胞癌切除後の予後予測 (2014)
  • Author(s): 兼清 信介、飯塚 徳男、恒富 亮一、徳光 幸生、橋本 憲輝、徳久 善弘、前田 祥成、飯田 通久、坂本 和彦、為佐 卓夫、岡 正朗
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会議場(京都)
  • Year and Date: 2014-04-03
• [Presentation] 血清メチル化遺伝子による肝細胞癌切除後の予後予測 (2013)
  • Author(s): 兼清信介、飯塚徳男 他
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場
• [Presentation] メチル化遺伝子に基づいた切除後肝細胞癌の肝内早期再発予測 (2013)
  • Author(s): 兼清信介、飯塚徳男 他
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
• [Patent(Industrial Property Rights)] 情報処理装置と情報処理プログラム並びに情報処理方法 (2014)
  • Inventor(s): 浜本義彦、飯塚徳男
  • Industrial Property Rights Holder: 国立大学法人山口大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-07-18
  • Acquisition Date: 2014-12-26