共突变基因与晚期非小细胞肺癌靶向治疗预后生存的相关性分析  

Correlation between co-mutated genes and prognosis of targeted therapy in advanced non-small cell lung cancer

作　　者：杨远雪 蔡志强[1] 谢茜 王梦[1] 李娜 林陈石 李岩 蔡君[1] 杨继元[1] YANG Yuanxue;CAI Zhiqiang;XIE Xi;WANG Meng;LI Na;LIN Chenshi;LI Yan;CAI Jun;YANG Jiyuan(Department of Medical Oncology,the First Affiliated Hospital of Yangtze University,Hubei Jingzhou 434000,China)

机构地区：[1]长江大学附属第一医院肿瘤科,湖北荆州434000

出　　处：《现代肿瘤医学》2022年第19期3503-3509,共7页Journal of Modern Oncology

基　　金：湖北省自然科学基金(编号:2019CFB817)。

摘　　要：目的:进一步验证晚期表皮生长因子受体(epidermal growth factor receptor,EGFR)突变非小细胞肺癌(non-small cell lung cancer,NSCLC)靶向治疗预后生存情况,探讨共突变基因与患者预后生存的相关性。方法:回顾性分析2016年01月至2019年12月我院经病理确诊为晚期NSCLC,二代测序(next-generation sequencing,NGS)为EGFR突变阳性,且使用表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)一代药物作为一线治疗的102例患者的病历和随访资料。收集其临床病理特征、治疗前的检验结果、基因检测报告、共突变基因和随访信息。采用Cox回归模型分析共突变基因与无疾病进展生存期(progression-free survival,PFS)的相关性。通过基因表达谱数据动态分析(Gene Expression Profiling Interactive Analysis,GEPIA)公共数据库分析磷脂酞肌醇-3-激酶催化亚单位α基因(phosphoinositide-3-kinase catalytic alpha polypeptide gene,PIK3CA)、人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)、间质表皮转化因子(mesenchymal-epithelial transition factor,MET)三种共突变基因与肺癌总生存期(overall survival,OS)和无病生存期(disease-free survival,DFS)的相关性。结果:102例一线靶向治疗的晚期NSCLC患者中位PFS为10个月。单因素分析表明,EGFR突变合并PIK3CA突变的患者一线靶向治疗的中位PFS为8个月,不合并PIK3CA突变患者的中位PFS为11个月,差异有统计学意义(P=0.037);EGFR突变合并T790M突变患者的中位PFS为6个月,不合并T790M突变患者中位PFS为10个月,差异有统计学意义(P=0.043);EGFR突变合并HER-2扩增的患者中位PFS为7个月,不合并HER-2扩增的患者中位PFS为10个月,差异有统计学意义(P=0.048);EGFR突变合并MET扩增的患者中位PFS为3个月,不合并MET扩增的患者中位PFS为10个月,差异有统计学意义(P=0.001)。多因素分析显示,合并PIK3CA突变(HR=0.536,95%CI:0.Objective:To further verify the prognosis and survival of advanced EGFR mutated non-small cell lung cancer(NSCLC)after targeted therapy,and to explore the correlation between co-mutated genes and prognosis and survival of patients.Methods:It was retrospectively analyzed that the medical records and follow-up data of 102 patients with epidermal growth factor receptor(EGFR)mutation positive tested by next-generation sequencing(NGS),received first-line targeted therapy with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)and pathologically diagnosed as advanced non-small cell lung cancer(NSCLC),who were admitted in our hospital from January 2016 to December 2019.Clinicopathological features,pretreatment test results,genetic test reports,comutant genes and follow-up information were collected in the analysis.Cox regression model was used to analyze the influence of comutant genes on the prognosis of progression-free survival(PFS),while the Gene Expression Profiling Interactive Analysis(GEPIA)public database was used to analyze the correlation between phosphoinositide-3-kinasecatalytic alpha polypeptide gene(PIK3CA),human epidermal growth factor receptor-2(HER-2)and mesenchymal-epithelial transition factor(MET)comutations and the prognosis(OS and DFS)of lung cancer.Results:The median progression-free survival(mPFS)of 102 patients with advanced NSCLC treated with first-line targeted therapy was 10 months.The univariate analysis showed that the mPFS of patients with EGFR mutation combined with PIK3CA mutation was 8 months after first-line targeted therapy,and that of patients without PIK3CA mutation was 11 months.The difference was statistically significant(P=0.037).The mPFS of patients with EGFR mutation combined with threonine790 to methionine(T790M)mutation was 6 months,and that of patients without T790M mutation was 10 months.The difference was statistically significant(P=0.043).The mPFS of patients with EGFR mutation combined with HER-2 amplification was 7 months,and that of pat

关 键 词：EGFR EGFR-TKI 非小细胞肺癌 耐药 

分 类 号：R734.2[医药卫生—肿瘤]