| 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 |
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| 引用本文： | 杨远雪,蔡志强,谢 茜,王 梦,李 娜,林陈石,李 岩,蔡 君,杨继元.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[J].现代肿瘤医学,2022,0(19):3503-3509. |
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| 作者姓名： | 杨远雪 蔡志强 谢 茜 王 梦 李 娜 林陈石 李 岩 蔡 君 杨继元 |
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| 作者单位： | 长江大学附属第一医院肿瘤科，湖北 荆州 434000 |
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| 基金项目： | 湖北省自然科学基金（编号:2019CFB817） |
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| 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:0.302~0.951,P=0.033）、HER-2扩增（HR=0.359,95%CI:0.142~0.909,P=0.031）、MET扩增（HR=0.139,95%CI:0.042~0.464,P=0.001）是PFS的独立预后因素。PIK3CA基因与晚期NSCLC的DFS有相关性（P<0.05）。结论:晚期NSCLC靶向治疗前合并PIK3CA突变、HER-2扩增、MET扩增是患者PFS的独立影响因素。
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| 关 键 词： | EGFR EGFR-TKI 非小细胞肺癌 耐药 |
Correlation between co-mutated genes and prognosis of targeted therapy in advanced non-small cell lung cancer |
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| YANG Yuanxue,CAI Zhiqiang,XIE Xi,WANG Meng,LI Na,LIN Chenshi,LI Yan,CAI Jun,YANG Jiyuan.Correlation between co-mutated genes and prognosis of targeted therapy in advanced non-small cell lung cancer[J].Journal of Modern Oncology,2022,0(19):3503-3509. |
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| Authors: | YANG Yuanxue CAI Zhiqiang XIE Xi WANG Meng LI Na LIN Chenshi LI Yan CAI Jun YANG Jiyuan |
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| Affiliation: | Department of Medical Oncology,the First Affiliated Hospital of Yangtze University,Hubei Jingzhou 434000,China. |
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| Abstract: | 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 patients without HER-2 amplification was 10 months.The difference was statistically significant（P=0.048).The mPFS of patients with EGFR mutation combined with MET amplification was 3 months,while that of patients without MET amplification was 10 months.The difference was statistically significant（P=0.001).In multivariate analysis,combined PIK3CA mutation（HR=0.536,95%CI:0.302~0.951,P=0.033),HER-2 amplification（HR=0.359,95%CI:0.142~0.909,P=0.031),MET amplification（HR=0.139,95%CI:0.042~0.464,P=0.001) were independent prognostic factors for PFS.There was significant correlation between PIK3CA and DFS of lung cancer（P<0.05).Conclusion:The combination of PIK3CA mutation,HER-2 amplification and MET amplification before targeted therapy were independent influencing factors for PFS of targeted therapy. |
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| Keywords: | EGFR EGFR-TKI non-small cell lung cancer resistance |
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