循环肿瘤DNA与EGFR、KRAS、NRAS突变型可切除非小细胞肺癌的病理关系  

Pathological relationship between circulating tumor DNA and EGFR,KRAS and NRAS mutant resectable non-small cell lung cancer

作　　者：王磊 刘先 吴清辉 高珂[1] WANG Lei;LIU Xian;WU Qing-hui;GAO Ke(Department of Cardiothoracic Surgery,Chengdu Second People's Hospital,Chengdu Sichuan 610017,China)

机构地区：[1]成都市第二人民医院胸心外科,四川成都610017

出　　处：《局解手术学杂志》2025年第2期154-158,共5页Journal of Regional Anatomy and Operative Surgery

基　　金：四川省科技创新人才项目(2021JDRC0017)。

摘　　要：目的 探讨循环肿瘤DNA(ctDNA)与表皮生长因子受体基因(EGFR)、Kirsten大鼠肉瘤病毒癌基因(KRAS)、神经母细胞瘤RAS病毒致癌基因(NRAS)突变型可切除非小细胞肺癌(NSCLC)患者临床病理特征的关系。方法 纳入在我院接受手术切除并且在生物库中有匹配血浆样本的36例NSCLC患者进行突变分析。使用肽核酸钳制PCR法分析血浆ctDNA和活检组织EGFR、KRAS、NRAS突变,探讨血浆ctDNA脱落与患者临床病理特征的关系。结果 36例患者活检组织和血浆样本中EGFR、KRAS、NRAS的一致性分别为63.89%(23/36)、88.89%(32/36)、86.11%(31/36)。在突变型肿瘤中,血浆ctDNA中EGFR、KRAS、NRAS突变检测的敏感度分别为23.53%(4/17)、33.33%(2/6)、40.00%(2/5)。在腺癌患者中,血浆ctDNA脱落与较高的肿瘤分期、N分期、TNM分期、肿瘤坏死率、10HPFs核分裂象及较大的肿瘤最大直径、肿瘤体积有关(P<0.05)。在肺腺癌患者亚组分析中,ctDNA脱落与较高的N分期、血管浸润率、肿瘤坏死率、10HPFs核分裂象及更大的肿瘤最大直径、肿瘤体积显著相关(P<0.05)。结论 肺腺癌ctDNA脱落与原发性肿瘤的直径、体积以及侵袭性组织学特征(如坏死和高核分裂象)有关。Objective To investigate the relationship between the circulating tumor DNA(ctDNA)and the clinicopathological features of epidermal growth factor receptor gene(EGFR),Kirsten rat sarcoma viral oncogene(KRAS),and neuroblastoma RAS viral oncogene(NRAS)in patients with mutant resectable non-small cell lung cancer(NSCLC).Methods Thirty-six patients with NSCLC who underwent surgical resection in our hospital and had matched plasma samples in the biobank were included for mutation analysis.The EGFR,KRAS and NRAS mutations of plasma ctDNA and biopsy tissue were analyzed by peptide nucleic acid clamp PCR to explore the relationship between plasma ctDNA shedding and clinicopathological features of patients.Results The consistency of EGFR,KRAS and NRAS in biopsy tissue and plasma samples of 36 patients was 63.89%(23/36),88.89%(32/36)and 86.11%(31/36),respectively.In mutant tumors,the sensitivity of EGFR,KRAS and NRAS mutation detection in plasma ctDNA was 23.53%(4/17),33.33%(2/6)and 40.00%(2/5),respectively.In patients with adenocarcinoma,plasma ctDNA shedding was associated with higher tumor stage,N stage,TNM stage,tumor necrosis rate,mitotic count 10HPFs,larger maximum tumor diameter and tumor volume(P<0.05).In subgroup analysis of lung adenocarcinoma patients,ctDNA shedding was significantly associated with higher N stage,vascular invasion rate,tumor necrosis rate,and mitotic count 10HPFs,as well as larger maximum tumor diameter and tumor volume(P<0.05).Conclusion The shedding of ctDNA in lung adenocarcinoma is associated with primary tumor diameter,volume,and aggressive histological features(such as necrosis and high mitotic count).

关 键 词：非小细胞肺癌 循环肿瘤DNA 基因突变 肽核酸钳制PCR法 

分 类 号：R734.1[医药卫生—肿瘤]