Establishment of novel less-invasive diagnostic method using plasma cell-free DNA in small-cell lung cancer

• Project/Area Number: 16K07154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: National Cancer Center Japan
• Principal Investigator: Umemura Shigeki 国立研究開発法人国立がん研究センター, 東病院, 医員 (80623967)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 小細胞肺癌 / 低侵襲 / 遺伝子解析 / 遊離DNA / 代謝解析 / メタボローム解析 / バイオマーカー / 血漿 / 化学療法 / DNA / 代謝バイオマーカー / ゲノム解析 / 医療・福祉 / 癌 / ゲノム

Outline of Final Research Achievements

We extracted cell-free DNA from plasma samples of small-cell lung cancer (SCLC) patients and performed targeted capture sequencing. In 60% of plasma samples, we could successfully identify genetic mutations detected by tumor biopsy samples. Overall survival was poorer and serum LDH level was higher for SCLC patients whose plasma samples were successful for genetic analysis, suggesting aggressive features for these patients. In this study, we could suggest the efficacy of less-invasive genetic analysis method using plasma samples in rapid growing SCLC. In addition, we compared the plasma levels of metabolites between SCLC patients and patients with no malignancies. Plasma levels of cis-aconitic acid and isocitric acid were significantly higher in SCLC patients, suggesting plasma metabolites could be a minimally-invasive and effective biomarkers in SCLC.

Academic Significance and Societal Importance of the Research Achievements

急速に進行し予後不良な小細胞肺癌では、病変の一部を採取して詳しく調べる検査が困難なケースがある。このような症例に対して、血漿を用いた低侵襲な遺伝子解析の有用性が示唆されたため、社会的意義は大きいと考えられる。一方、代謝産物を指標としたバイオマーカー開発は、今後の発展性が期待される領域であるが、実施例がほとんどないのが現状である。その中で、本研究にて、小細胞肺癌において血漿代謝産物が有効なバイオマーカーとなる可能性が示唆されたため、他がん腫への応用や今後のバイオマーカー開発の進展に貢献できる可能性があり、学術的意義は高いと考えられる。

Research Products

• [Presentation] Impact of large-scale nationwide genomic screening project for small cell lung cancer (LC-SCRUM-Japan) (2019)
  • Author(s): Naoki Furuya, Shigeki Umemura, Hibiki Udagawa, Tadasuke Shimokawaji, Takashi Seto, Haruko Daga, Kosuke Tsuruno, Masato Shingyoji, Satoshi Hara, Haruyasu murakami, Hiroshi Yokouchi, Shingo Matsumoto, Koichi Goto
  • Organizer: 2019 ASCO annual meeting
  • Int'l Joint Research