肿瘤标志物TTF-1预测肺腺癌EGFR突变模型的构建及初步评估

Establishment and Preliminary Evaluation of Tumor Marker TTF-1 for Predicting EGFR Mutation in Lung Adenocarcinoma

目的:构建肿瘤标志物甲状腺转录因子-1(TTF-1)预测肺腺癌表皮生长因子受体(EGFR)突变模型,并探讨其对肺腺癌患者EGFR基因突变的预测价值。方法:选取2018年6月至2019年5月本院胸心外科收治的120例初治肺腺癌患者作为受试对象,根据EGFR基因表型检测结果将其分为EGFR基因野生(非突变)组72例和EGFR基因突变组48例。使用En Vision免疫组化法检测TTF-1表达,使用扩增阻滞突变系统法检测EGFR基因外显子18、19、20、21突变,并采用多因素Logistic回归分析影响肺腺癌患者EGFR基因突变的相关因素。结果:EGFR基因突变组肺腺癌患者TTF-1表达阳性率明显高于EGFR基因野生组患者(P<0.05)。EGFR基因突变情况与肺腺癌患者年龄、功能状态(PS)评分及肿瘤位置均无关(P>0.05),与肺腺癌患者性别、吸烟史及TNM分期均有关(P<0.05)。多因素Logistic回归分析发现,TNM分期、TTF-1表达是肺腺癌患者发生EGFR基因突变的独立危险因素(P<0.05),而性别、吸烟史与肺腺癌患者EGFR基因突变发生无独立相关性(P>0.05)。TTF-1表达单独及其与临床病理参数联合预测肺腺癌患者发生EGFR基因突变的灵敏度、特异度、准确度、阳性预测值及阴性预测值高低依次为:TTF-1、性别、吸烟、TNM分期四者联合预测,TTF-1、性别、吸烟三者联合预测,TTF-1联合性别预测,TTF-1表达单独预测。结论:TTF-1阳性与患者EGFR基因突变有关,TTF-1表达联合其他因素可能更有助于预测肺腺癌患者EGFR基因突变状态。

Objective:To explore the establishment and preliminary evaluation of a model for predicting epidermal growth factor receptor(EGFR)mutation in lung adenocarcinoma by thyroid transcription factor-1(TTF-1),a tumor marker.Methods:120 patients with primary lung adenocarcinoma admitted to our hospital from June 2018 to May 2019 were selected as subjects.According to the results of EGFR genotype detection,they were divided into wild(non-mutation)group of EGFR gene(72 cases)and mutation group of EGFR gene(48 cases).TTF-1 expression was detected by En Vision immunohistochemistry,mutations in exons 18,19,20 and 21 of EGFR gene were detected by amplification-blocked mutation system,and multivariate logistic regression was used to analyze the related factors affecting EGFR gene mutation in patients with lung adenocarcinoma.Results:The positive rate of TTF-1 expression in lung adenocarcinoma patients with EGFR gene mutation was significantly higher than that in wild EGFR gene group(P<0.05).The mutation of EGFR gene was not related to age,performance status(PS)score and location of lung adenocarcinoma(P>0.05),but related to sex,smoking history and TNM stage of lung adenocarcinoma(P<0.05).Multivariate logistic regression analysis showed that TNM stage and TTF-1 expression were independent risk factors for EGFR gene mutation in lung adenocarcinoma patients(P<0.05),while gender,smoking history and EGFR gene mutation in lung adenocarcinoma patients had no independent correlation(P>0.05).The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of TTF-1 expression alone and in combination with clinicopathological parameters in predicting EGFR gene mutation in lung adenocarcinoma patients were the combination prediction of TTF-1,sex,smoking and TNM stage,the combination prediction of TTF-1,sex and smoking,the combination prediction of TTF-1 and sex,and the separate prediction of TTF-1 expression.Conclusions:TTF-1 positive is associated with EGFR gene mutation.TTF-1 expression combined with other factors may be more helpful in predicting EGFR gene mutation in patients with lung adenocarcinoma.