| Project/Area Number |
20K16685
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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 52040:Radiological sciences-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
Obara Hideki 弘前大学, 医学部附属病院, 放射線技師 (10776610)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 前立腺癌 / メタボロミクス / 個別化放射線治療 / 急性期有害事象 |
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| Outline of Research at the Start |
現在の放射線治療戦略は癌腫により治療方針が決定するが，個別の生物学的応答は含まれていない．患者における放射線感受性の違いを把握し個別化放射線治療を行うべきであるが，未だシステムが不十分である．近年，代謝生物学分野ではメタボロミクス解析によって体内環境を把握する研究が盛んである．前立腺癌に対してこの技術を利用し，非侵襲的に採取可能な尿に着目して，これまでに報告のないメタボロミクスを導入した個別化放射線治療Metabolomics-guided radiation therapyを提案するため，基礎研究と後方視的解析を実施する．得られる情報は，癌の放射線治療の効果向上に貢献することが期待される．
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| Outline of Final Research Achievements |
In this study, a retrospective analysis was conducted to predict acute AEs through VMAT for prostate cancer according to urinal metabolomic molecules. Urine samples from a total of 11 patients with prostate cancer who were administered treatment via VMAT (76 Gy/38 fractions) were collected. The findings revealed seven patients with genitourinary toxicity (Grade 1) and four patients with nonAEs. Thereafter, the 630 urinal metabolites were analyzed using a mass spectrometer, and 234 relevant molecules were extracted from the absolute quantified values of metabolites using the MetaboINDICATOR. In the Grade 1 group of acute AEs, a significant negative correlation (r=－0.297, p<0.05) between the number of fractions by VMAT and total phospholipase A2 activity in the urine was noted. Additionally, a decrease in PC aa C40:1 was demonstrated in Grade 1 patients. These results suggest that specific lipids in urinal metabolites have the potential to be predictive biomarkers for acute AEs in VMAT.
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| Academic Significance and Societal Importance of the Research Achievements |
限局性前立腺癌患者に対する放射線治療は，急性期有害事象を生じることが多く，その後の治療やQOLに影響を及ぼす可能性がある．照射回数と尿中の総ホスホリパーゼA2活性との間に有意な負の相関(r=-0.297，p<0.05)を認め，PC aa C40:1の減少が示された．PC aa C40:1は照射1回目および30回目において急性期有害事象発生に関して，高い特異性と感度を示した．ゆえに，尿中代謝産物中の特異的脂質は，VMATにおける急性期有害事象の予測バイオマーカーとなる可能性が示唆された．個々の患者に合わせた放射線治療を行う一助となる．
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