2022 Fiscal Year Research-status Report
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 Institution | Kanazawa University |
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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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| Keywords | cell free tumor DNA / Liquid biopsy / EGFR mutation / adjuvant chemotherapy / lung cancer |
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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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| Causes of Carryover |
本研究にあたって最も経費を要すると考えられるのは、次世代シークエンサーを用いたDNA, RNA解析やエクソソーム中のタンパク質量分析であるが、いずれも令和５年度内に施行予定となった。これには令和５年度の請求金額と合わせて200万円の経費使用を見込んでいる。これまで半年間は、先に臨床的背景の検討をおこなったため、次年度への持ち越しが発生した。
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