術前liquid biopsyを用いたゲノム・RNA発現解析による肺癌術後の個別化医療の探索
Project/Area Number |
22K20788
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0901:Oncology and related fields
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Research Institution | Kanazawa University |
Principal Investigator |
木場 隼人 金沢大学, 医薬保健学総合研究科, 特任助教 (80967886)
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Project Period (FY) |
2022-08-31 – 2024-03-31
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Project Status |
Granted (Fiscal Year 2022)
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Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | cell free tumor DNA / Liquid biopsy / EGFR mutation / adjuvant chemotherapy / lung cancer / liquid biopsy / 肺癌 / 術後化学療法 |
Outline of Research at the Start |
早期肺癌では外科的切除で根治が望まれるが、残念ながら再発することがあり新規のリスク評価法・治療標的を探索することが重要である。 血中遊離DNA(cfDNA)やmicro RNA(miRNA)を用いて癌の遺伝子異常を検出する方法が発展している。我々は以前に、診断時の腫瘍組織で認められずcfDNAで検出された遺伝子変異が、経過で出現した転移巣で検出されることを報告した。本研究では、術前のcfDNAとmiRNAを解析し、再発時期との関連や手術検体から得られた組織由来のRNA発現パターンとの関連を検討する。本解析から新たなバイオマーカーの創出や治療標的を発見し、オーダーメイドの術後療法の確立を目指す。
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Outline of Annual Research Achievements |
We enrolled patients with lung cancer who underwent surgery without preoperative chemotherapy at the Kanazawa University Hospital. We extracted cfDNA from the plasma within 7 days before surgery using Qiagen and measured its concentration using Qubit High sensitivity. CfDNA from patients with EGFR-mutated NSCLC was analyzed using Digital Droplet PCR.We retrospectively collected patient characteristics including EGFR mutation status, DFS, and OS. Written informed consent was obtained from all the patients. A total of 285 patients were enrolled in this study. The median age was 71 years, and 62% of the patients were male. EGFR mutations were present in 42% of patients with adenocarcinoma. The EGFR-positive cases were predominantly female, and 80% were pStage 1. No significant correlation between cfDNA concentration and OS in pStage 0 to 3. We analyzed common EGFR mutations and detected L858R mutations in 16 of 56 patients and deletion 19 in 7 of 32 patients. CfDNA-positive patients had a significantly shorter DFS than cfDNA-negative patients. There was no correlation between preoperative cfDNA concentration and prognosis in our study, probably because cfDNA other than that derived from the tumor was also detected. In our study, EGFR-mutated surgical patients at stages II and III tended to have shorter DFS than EGFR wild-type patients. Postoperative osimertinib administration may be a better indication for ctDNA-positive cases.
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
上記のごとく血清由来のcell free DNAを用いた解析と、臨床情報の解析は予定通り終了し2つの学会報告することができた。ただし後述のごとくシークエンスやタンパク、RNA発現解析が本年後に入ってから開始予定となっており、遅延を認めている作業もある。順次開始予定である。
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Strategy for Future Research Activity |
研究計画にある通り、血清中のcell free RNAやエクソソーム中のRNAやタンパクの抽出を行い、それらの解析を行う予定である。現在エクソソーム中の質量分析を施行中である。
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Report
(1 results)
Research Products
(2 results)