非小细胞肺癌EGFR突变亚型的临床病理和预后意义  

Clinicopathological and prognostic significance of EGFR mutant subtypes in patients with non-small cell lung cancer

作　　者：赖淼 景鑫 李桂珍 李怡 Lai Miao;Jing Xin;Li Guizhen;Li Yi(Department of Thoracic Surgery,Second Affiliated Hospital of Air Force Military Medical University,Xi′an 710038,China)

机构地区：[1]空军军医大学第二附属医院胸腔外科,西安710038

出　　处：《中华肺部疾病杂志（电子版）》2024年第5期731-737,共7页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：陕西省重点研发计划项目(2022SF-346)。

摘　　要：目的分析非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)表皮生长因子受体(epidermal growth factor receptor,EGFR)突变亚型的临床病理和预后意义。方法选择2016年1月至2022年6月我院收治的接受EGFR基因检测127例突变型晚期NSCLC患者。采用直接测序法进行EGFR突变检测,根据突变位点分为四组:外显子(E)18突变组、E19突变组、E20突变组、E21突变组。根据突变模式将E19缺失突变分为三种亚型组:密码子缺失(codon deletion,CD)组、密码子替换和跳变(codon substitutions and skipping,CSS)组、CD或CSS加单核苷酸变异(single nucleotide variants,SNV)(CD/CSS+SNV)组。主要观察指标为无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。结果EGFR突变中,常见E19缺失73例(57.48%),其次为E21突变40例(31.50%),E18突变6例(4.72%),E20突变8例(6.30%)。患者中位随访时间为22.23个月(3.02~60个月)。E19突变患者的中位PFS和中位OS时间最长(13个月、30.59个月),长于E18突变(9个月、10.85个月)、E20突变(10个月、19.48个月)和E21突变(10个月、16.92个月)(P<0.05)。多因素分析模型中,E19突变是NSCLC患者PFS和OS的影响因素(P<0.05)。E19突变患者中,CD/CSS+SNV组中位PFS和中位OS(43个月、51.25个月)长于CD组(12个月、29.87个月)和CSS组(10个月、20.66个月)(P<0.05)。CD/CSS+SNV组缺失碱基和缺失氨基酸数(12.80±2.88个、4.40±0.91个)低于CD组(14.87±0.88个、4.98±0.33个)和CSS组(16.73±3.35个、5.81±0.98个)(P<0.05)。结论与E18/20/21突变患者相比,E19缺失突变患者PFS和OS预后好,提示E19缺失是EGFR突变型NSCLC患者PFS和OS的预测因子。E19突变患者中CD/CSS SNV与PFS和OS长显著相关。Objective To investigate the prognostic value of plasma circulating tumor DNA(EGFR)in epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)in patients with advanced nonsmall cell lung cancer(NSCLC).Methods This study reviewed 127 patients with mutant advanced NSCLC who underwent EGFR gene testing in our hospital between January 2016 and June 2022.EGFR mutation was detected by direct sequencing method and divided into four groups according to mutation sites:exon(E)18 mutant group,E19 mutant group,E20 mutant group,and E21 mutant group.In addition,E19 deletion mutations were divided into three subtype groups based on mutation patterns:codon deletion(CD),codon substitution and skipping(CSS),and CD or CSS plus single nucleotide variant(SNV)(CD/CSS+SNV).The main outcome measures were progression-free survival(PFS)and overall survival(OS).Results Among EGFR mutations,E19 deletion was the most common73cases(57.48%),followed by E21 mutation 40cases(31.50%),E18 mutation 6cases(4.72%),and E20 mutation 8 cases(6.30%).The median follow-up time for all NSCLC patients was 22.23 months(range 3.02 to 60 months).Patients with E19 mutation had the longest median PFS and OS duration(13 months,30.59 months),and were significantly longer than those with E18 mutation(9 months,10.85 months),E20 mutation(10 months,19.48 months),and E21 mutation(10 months,16.92 months)(P<0.05).In the multivariate analysis model,E19 mutation was an independent influencing factor for PFS and OS in NSCLC patients(P<0.05).Among patients with E19 mutations,the median PFS and median OS(43 months,51.25 months)in the CD/CSS+SNV group were significantly longer than those in the CD group(12 months,29.87 months)and CSS group(10 months,20.66 months)(P<0.05).The number of missing bases and missing amino acids in CD/CSS+SNV group(12.80±2.88,4.40±0.91)were significantly lower than those in CD group(14.87±0.88,4.98±0.33)and CSS group(16.73±3.35,5.81±0.98)(P<0.05).Conclusion Compared with patients with E18/20/21 mutations,patients with E19 deletion

关 键 词：非小细胞肺癌 表皮生长因子受体突变亚型 外显子19 缺失突变 预后 

分 类 号：R734.2[医药卫生—肿瘤]