基于循环肿瘤DNA分析肺癌患者EGFR共突变基因的临床应用  

Clinical application of EGFR co-mutation gene analysis in lung cancer patients based on circulating tumor DNA

作　　者：李丹 闪亮 马丽芳 王佳谊 Li Dan;Shan Liang;Ma Lifang;Wang Jiayi(Department of Clinical Laboratory Medicine,Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai200032,China)

机构地区：[1]上海市胸科医院/上海交通大学医学院附属胸科医院检验科,上海200032

出　　处：《中华检验医学杂志》2024年第11期1286-1291,共6页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金(82173015,82273139,82200245,82302641)。

摘　　要：目的基于循环肿瘤DNA(ctDNA)分析晚期非小细胞肺癌患者表皮生长因子受体(EGFR)伴随抑癌基因P53(TP53)及磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)或SMAD家族成员4(SMAD4)基因突变在临床应用中的价值。方法单中心、回顾性研究。筛选2022年6月至2024年1月就诊于上海市胸科医院的非小细胞肺癌患者,收集患者靶向治疗前的外周血,分离细胞游离DNA(cfDNA)及白细胞DNA,进行二代测序,比对分析后获取ctDNA数据,按照美国分子病理协会/美国临床肿瘤学会/美国病理学家协会联合制定的体细胞变异解读指南对患者基因变异进行分析。采用卡方检验及Kaplan-Meier生存曲线评估EGFR基因突变患者及同时伴随其他基因突变患者的靶向治疗部分缓解(PR)率。结果126例患者中仅携带EGFR突变率为46.0%(58/126),PR率为74.1%(43/58);EGFR、TP53双重突变率为37.3%(47/126),PR率53.2%(25/47);EGFR、TP53突变同时伴随PIK3CA或SMAD4突变率16.7%(21/126),PR率28.6%(6/21),且3组间无进展生存曲线差异有统计学意义(χ^(2)=23.81,P<0.01)。结论基于ctDNA的二代测序检测技术可检出伴随EGFR突变的TP53、PIK3CA或SMAD4等基因突变,多重基因突变是患者PR率及无进展生存曲线较差的重要因素。Objective To investigate the clinical significance of gene mutations in epidermal growth factor receptor(EGFR),tumor suppressor gene P53(TP53),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),or SMAD family member 4(SMAD4)in patients with advanced non-small cell lung cancer(NSCLC)based on circulating tumor DNA(ctDNA)analysis.Methods A single-center,retrospective study was conducted among patients with NSCLC who visited Shanghai Chest Hospital from June 2022 to January 2024.Peripheral blood was collected from patients prior to targeted therapy,and cell-free DNA(cfDNA)and leukocyte DNA were isolated for next-generation sequencing.ctDNA data was obtained through comparative analysis.Patient gene mutations were analyzed according to the guidelines for the interpretation of somatic variants jointly established by the Association for Molecular Pathology/College of American Pathologists/American Society of Clinical Oncology.Analysis of variance and Kaplan-Meier survival curves were applied to assess the partial response(PR)rate among patients with EGFR gene mutations and those with concurrent mutations in other genes.Results Among 126 patients,the rate of carrying only EGFR mutations was 46.0%(58/126),with a PR rate of 74.1%(43/58).The rate of double mutations in EGFR and TP53 was 37.3%(47/126),with a PR rate of 53.2%(25/47).The rate of triple mutations in EGFR,TP53,and concurrent mutations in PIK3CA or SMAD4 was 16.7%(21/126),with a PR rate of 28.6%(6/21).The comparison of progression-free survival curves among the three groups showed a statistically significant difference(χ^(2)=23.81,P<0.01).Conclusions next-generation sequencing detection technology based on ctDNA can detect concurrent mutations in TP53,PIK3CA,or SMAD4 along with EGFR mutations.Multiple gene mutations are significant factors for poor PR rates and progression-free survival curves in patients.

关 键 词：癌 非小细胞肺 二代测序 受体 表皮生长因子 

分 类 号：R734.2[医药卫生—肿瘤]