| Project/Area Number |
17K07197
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor diagnostics
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 明美 佐賀大学, 医学部, 助教 (20568357)
中村 朝美 佐賀大学, 医学部, 助教 (90457490)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | circulating free DNA / EGFR / extracellular vesicle / circulating tumor DNA / EGFR T790M / metastasis / 液体生検 / 肺癌 |
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| Outline of Final Research Achievements |
We reported bimodal peaks of long fragment circulating free DNA (cfDNA) of 5 kb and short fragment cfDNA of 170 bp in patients with advanced lung cancer, and the amount of long fragment cfDNA is significantly higher in patients with distant metastasis. Long fragment cfDNA was found concomitant with extracellular vesicles (EVs). In human plasma samples, long fragment cfDNA was observed in the same fraction as long fraction detected from conditioned media, and short fragment cfDNA existed in the supernatant after centrifugation at 100,000g. Concentration of ctDNA in the supernatant was two times higher than that in plasma isolated by the conventional procedure. Long fragment cfDNA associated with tumor progression might therefore be released into peripheral blood, and it is possible that the long fragment cfDNA escapes degradation by co-existing with EVs. Examination of the biological characteristics of long fragment cfDNA is a logical subject of further investigation.
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| Academic Significance and Societal Importance of the Research Achievements |
circulating tumor DNA (ctDNA) を用いたliquid biopsyは世界中で注目され2016年9月米国ではFDAで承認された。しかし、薬剤耐性化後の組織は腫瘍不均一性が高く、再生検との耐性化遺伝子変異一致率は60-70%前後である。また、遠隔転移を伴わい局所進行がんでは、liquid biopsyによるctDNA検出率は依然として低い。至適治療を行うためにはliquid biopsyの診断精度の向上が望まれる。本研究の成果のより、ctDNAをより効率的に分離できればliquid biopsyの精度改善につながる。
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