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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

通过术前液体活检进行基因组/RNA表达分析探索肺癌术后个体化医疗

基本信息

批准号：
22K20788
负责人：
木場隼人
金额：
$ 1.83万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2022
资助国家：
日本
起止时间：
2022-08-31 至 2024-03-31
项目状态：
已结题

项目摘要

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.

我们招募了在金泽大学附属医院接受手术但未进行术前化疗的肺癌患者，使用Qiagen从术前7天内的血浆中提取cfDNA，并使用Qubit High sensitivity测量其浓度。采用Digital Droplet PCR技术检测EGFR突变的NSCLC患者的CfDNA，回顾性收集患者的EGFR突变状态、DFS和OS等特征，并获得所有患者的书面知情同意书，共纳入285例患者。中位年龄为71岁，62%的患者为男性。42%的腺癌患者存在EGFR突变。EGFR阳性病例主要为女性，80%为pStage 1。在pStage 0至3中cfDNA浓度与OS之间没有显著相关性。我们分析了常见的EGFR突变，在56例患者中检测到16例L858R突变，在32例患者中检测到7例缺失19。cfDNA阳性患者的DFS明显短于cfDNA阴性患者。在我们的研究中，术前cfDNA浓度与预后无关，可能是因为还检测到了肿瘤来源以外的cfDNA。在我们的研究中，EGFR突变的II期和III期手术患者的DFS往往比EGFR野生型患者短。术后给予奥希替尼可能是ctDNA阳性病例的更好适应症。