| Project/Area Number |
18K15326
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
Kei Sato 岩手医科大学, 医学部, 研究員 (60803591)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Circulating tumor DNA / 大腸癌 / 胃癌 / 食道癌 / 変異 / 消化管癌 / circulating tumor DNA / 遺伝子変異 / ctDNA / バイオマーカー / 次世代シークエンサー / デジタルPCR |
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| Outline of Final Research Achievements |
This study aimed to monitor therapeutic response using circulating tumor DNA (ctDNA) using digital PCR (dPCR) with individual tumor-specific mutations as identified from next generation sequencing (NGS) panel in patients with gastrointestinal cancer, including esophageal, gastric, and colorectal cancer. The dynamics of ctDNA level reflected therapeutic response more accurately compared with CT. In a relapsed patient, ctDNA elevation was observed several months before the recurrence was diagnosed by CT scan. The rate of positive ctDNA was about 80% in esophageal and colorectal cancer patients and about 40% in gastric patients, respectively. Multi-region samplings (three sites) from the resected specimens were also performed in colorectal and gastric cancers. The positive rate of ctDNA was higher in common mutations among three sites than non-common mutations. Our ctDNA monitoring system using may be useful for advanced gastrointestinal cancer patients.
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| Academic Significance and Societal Importance of the Research Achievements |
大腸癌、胃癌、食道癌を含む消化管癌において、原発巣の変異スクリーニングにより検出された症例特異的変異のctDNAモニタリングが、１）再発・再増大の早期検出、２）無再発の確認、３）正確な治療効果判定、に有用である可能性を明らかにした。ctDNA検査が日常臨床検査として普及するにはいくつかの問題点があるが、本研究のdPCRを用いたctDNA解析は低コストで短いturnaround timeで検査可能であり頻回な検査に適している。また、本研究を通して、組織特異的遺伝子パネルの有用性、１か所生検や少数変異で効率的なctDNAモニタリングが十分可能であることを示した。
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