2022 Fiscal Year Final Research Report
Development of modified nucleoside profiling methods in precision medicine
| Project/Area Number |
20K06997
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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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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 修飾核酸 / 修飾ヌクレオシド / LC-MS/MS / プロファイリング / 安定同位体 / バイオマーカー / 肺がん / ROC曲線 |
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| Outline of Final Research Achievements |
The purpose is to develop a new disease diagnostic method by modified nucleosides profile using LC-MS/MS. Modified nucleosides for standard and its stable isotopes for internal standard were synthesized in this study. As a result, it was possible to prepare a standard curve for modified nucleosides, which could not be quantified before, and to achieve precise quantification in human plasma.
The constructed quantitative system was applied to lung cancer patient plasma samples. A logistic regression analysis of the modified nucleoside quantification values showed a superior diagnostic model compared to existing lung cancer biomarkers.
This quantitative system for modified nucleosides with high comprehensiveness and high throughput is expected to play an important role in biomarker research and elucidation of pathology.
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| Free Research Field |
分析化学
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| Academic Significance and Societal Importance of the Research Achievements |
LC-MSを用いた修飾核酸の分析では、生体試料のマトリックス効果の影響が避けられず、分析適用範囲が限られていた。本研究によりこの問題を克服した修飾核酸一斉定量系を用いることで、バイオマーカー探索や病態把握が可能であることが示唆された。修飾核酸メタボロミクスに新たな方法を提案できるものと考えている。修飾核酸と生体内機能や疾患との関連の研究が多く進められており、網羅性およびハイスループット性の高い本定量系は様々な研究において重要な役割を担うと期待される。
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