| Project/Area Number |
18K16894
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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 56050:Otorhinolaryngology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
Kogo Ryunosuke 九州大学, 医学研究院, 共同研究員 (90529885)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ctDNA / リキッドバイオプシー / 頭頸部癌 / liquid biopsy |
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| Outline of Final Research Achievements |
Mutation analysis of tumor and normal (PBMC) DNAs of 26 patients with HNSCC was performed using a custom SCC panel. The identified individualized mutated genes were defined as ctDNA candidates. We performed frequent ctDNA monitoring via digital PCR (dPCR). TP53 was the most frequently mutated gene and was detected in 14 of 24 cases (62.5%), wherein 2 cases were excluded owing to the absence of tumor-specific mutations in the SCC panel. Six cases were excluded because of undesignable and unusable primer-probes for dPCR. Longitudinal ctDNA was monitored in a total of 18 cases. In 7 cases, ctDNA tested positive again or did not tested negative, and all 7 cases relapsed after initial treatment. In 11 cases, after initial treatment, ctDNA remained negative and patients were alive without recurrence. Patients who remained negative for ctDNA during follow-up after initial treatment (n = 11) had a significantly better prognosis than those who reverted to ctDNA positivity (n = 7; P < 0.0001).
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| Academic Significance and Societal Importance of the Research Achievements |
頭頸部癌には既存の腫瘍マーカーの測定についても有用性が確立されておらず、新規のバイオマーカーの同定が期待されている。ｃｔDNAはバイオマーカーとしての利用が期待されているが、頭頸部癌は変異スペクトラムが広く、特定の単一ctDNAをバイオマーカーとして使用することはできない。本手法によるctDNAモニタリングは頭頸部癌の臨床経過を鋭敏で反映していることがわかった。また、治療後に検出されるctDNAは再発や予後に寄与していることも判明した。今後、変異遺伝子のprimer-probeのライブラリの作成をすすめることでより簡易に安価でctDNAを臨床的バイオマーカーとして利用できる可能性がある。
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