标题：非小细胞肺癌EGFR基因突变的特征

      作者：于恪 1,2，张敏 1，杜秀芳 3    (1.深圳市第二人民医院呼吸内科，广东 深圳 518035；2.广州医科大学，广东 广州 510000；3.深圳市第六人民医院呼吸内科，广东 深圳 518052)

      卷次： 2018年29卷15期

      【摘要】 目的 分析非小细胞肺癌表皮生长因子受体(EGFR)基因突变的特征，为EGFR基因检测及靶向治疗提供指导。方法 收集深圳市第二人民医院2015年3月至2017年11月经病理确诊为非小细胞肺癌患者210例，采用突变阻滞扩增系统(ARMS)法检测其病理组织中EGFR基因突变的特征，并应用SPSS 19.0软件进行统计学分析。结果 210例非小细胞肺癌中EGFR基因突变103例，占49.1%，其中Exon 19(19del)和Exon 21(L858R)共占所有突变病例的 85.4%。腺癌突变率为 55.4%，女性突变率为 67.0%，不吸烟患者突变率为 59.1%，血清癌胚抗原(CEA)阳性组突变率为56.8%，分别与非腺癌突变率(3.8%)、男性突变率(34.5%)、吸烟患者突变率(33.7%)、CEA阴性组突变率(41.5%)比较差异均有显著统计学意义(P<0.01)；EGFR基因突变与年龄、临床分期无明显相关性(P>0.05)。亚组分析结果显示，19del和L858R突变率与性别、年龄、吸烟史、病理类型无明显相关性(P>0.05)。EGFR突变型患者血清CEA阳性率为 64.9%，明显高于野生型的 50.0%，差异有统计学意义(P<0.05)；Spearman相关分析结果显示，血清CEA水平与EGFR突变呈正相关(r=0.155，P<0.05)。多因素Logistic回归分析结果显示，女性、腺癌、CEA阳性是EGFR基因突变独立危险因素；预测突变Logistic回归模型通过ROC曲线分析结果显示，CEA联合临床特征预测突变 AUC (95%CI)可达 0.752 (0.687~0.816)，高于临床特征预测突变 AUC (95%CI)为 0.728(0.66~0.796)，差异有统计学意义(P<0.05)。结论 非小细胞肺癌中，腺癌、不吸烟、女性患者EGFR基因突变率较高，临床特征联合血清CEA可作为EGFR基因突变的预测指标。
      【关键词】 非小细胞肺癌；表皮生长因子受体；基因突变；肿瘤标记物
      【中图分类号】 R734.2 【文献标识码】 A 【文章编号】 1003—6350（2018）15—2076—05

Characteristics of EGFR gene mutation in non-small cell lung cancer.
YU Ke1,2, ZHANG Min 1, DU Xiu-fang 3.1. Department of Respiratory, the Second People's Hospital of Shenzhen City, Shenzhen 518035, Guangdong, CHINA;2. Guangzhou Medical University, Guangzhou 510000, Guangdong, CHINA; 3. Department of Respiratory, the Sixth People'sHospital of Shenzhen City, Shenzhen 518052, Guangdong, CHINA
【Abstract】 Objective To analyze the characteristics of epidermal growth factor receptor (EGFR) gene muta-tions in non-small cell lung cancer, and provide guidance for EGFR gene detection and targeted therapy. Methods A to-tal of 210 patients with non-small-cell lung cancer confirmed by pathology in the Second People's Hospital of ShenzhenCity from March 2015 to November 2017 were investigated in this study. Mutation-blocking amplification system(ARMS) was used to detect the mutations of EGFR gene in their pathological tissues, and statistical analysis was per-formed using SPSS19.0 software. Results In 210 cases of non-small cell lung cancer, 103 cases of EGFR gene muta-tion accounted for 49.1%, among which Exon 19 (19del) and Exon 21 (L858R) accounted for 85.4% of all mutations.The mutation rate of adenocarcinoma was 55.4% , the mutation rate of females was 67.0% , the mutation rate ofnon-smoking patients was 59.1%, and the mutation rate of serum carcinoembryonic antigen (CEA) positive group was56.8%, as compared to non-adenocarcinoma 3.8%, males 34.5%, smoking patients 33.7%, CEA negative group 41.5%(P<0.01). There was no significant correlation between EGFR gene mutation and age and clinical stage (P>0.05). Sub-group analysis showed that the mutation rates of 19del and L858R had no significant correlation with gender, age, smok-ing history and pathological types (P>0.05). The positive rate of serum CEA in patients with EGFR mutation was 64.9%,which was significantly higher than 50.0% of wild type (P<0.05). Spearman correlation analysis showed that serum CEAlevels were positively correlated with EGFR mutations (r=0.155, P<0.05). Multivariate logistic regression analysis showedthat female, adenocarcinoma and CEA positive were independent risk factors for EGFR gene mutations. The predicted mu-tation logistic regression model was analyzed by ROC curve and the results showed that the AUC (95% CI) for mutationprediction in CEA combined with clinical features was about 0.752 (0.687~0.816), significantly higher than AUC of 0.728(0.66~0.796) in clinical feature (P<0.05). Conclusion In non-small cell lung cancer, the rate of EGFR gene mutation ishigher in adenocarcinoma, non-smoking and female patients, and clinical features combined with serum CEA can beused as predictors of EGFR gene mutations.
      【Key words】 Non-small cell lung cancer; Epidermal growth factor receptor; Gene mutation; Tumor markers·论 著·doi:10.3969/j.issn.1003-6350.2018.15.002