Development of Liquid Biopsy System using cancer specific DNA methylation in colorectal cancer.

• Project/Area Number: 16K10549
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kitasato University
• Principal Investigator: Watanabe Masahiko 北里大学, 医学部, 教授 (80146604)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: stool / colorectal cacner / FIT / diagnosis / CDO1 / methylation / colorectal cancer / 大腸癌 / Cysteine dioxygenase 1 / メチル化 / Nested PCR / digital PCR / 便潜血 / liquid biopcy / stool test / blood test / DNA methylation / HOPX / 外科学 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Cancer detection rate was explored for stool samples of colorectal cancer (CRC).　The detection was performed with PCR detection system using cancer-specific methylation of CDO1 gene for CRC patients. Our methods were divised with nested outer PCR prior to inner Q-MSP/ddMSP, thus desiganted as NOPIQ/NOPID. In combination with fecal immunological test (FIT), NOPID can reach 100% of senstivity of CRC detection.

Academic Significance and Societal Importance of the Research Achievements

今回、独自に同定した癌特異的メチル化遺伝子 CDO1の高感度検出法として NOPIDを開発した。本法は、新しい技術なので特許に申請した。便検体における癌診断が既存の８０％を大きく上回り１００％に達した。以上から、大腸癌の便検査で見逃し症例が可及的に減少する可能性が示唆された。検診に応用することで大腸癌のスクリーニング検査として普及するポテンシャルがあると考えられる。今後は、前向き検証試験を行い実用性について再検していく予定である。

Research Products

• [Journal Article] Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer. (2017)
  • Author(s): Yokoi K, Yamashita K, Watanabe M.
  • Journal Title: Int J Mol Sci. Volume: 18 Issue: 4 Pages: 735-735
  • DOI: 10.3390/ijms18040735
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive molecular exploration identified promoter DNA methylation of the CRBP1 gene as a determinant of radiation sensitivity in rectal cancer. (2017)
  • Author(s): Yokoi K, Yamashita K, Ishii S, Tanaka T, Nishizawa N, Tsutsui A, Miura H, Katoh H, Yamanashi T, Naito M, Sato T, Nakamura T, Watanabe M.
  • Journal Title: Br J Cancer Volume: 116 Issue: 8 Pages: 1046-56
  • DOI: 10.1038/bjc.2017.65
  • Peer Reviewed / Open Access
• [Patent(Industrial Property Rights)] 癌の検出方法及びキット (2018)
  • Inventor(s): 渡邊昌彦
  • Industrial Property Rights Holder: 渡邊昌彦
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-146195
  • Filing Date: 2018