晚期肺腺癌患者血清中甲状腺转录因子-1表达与表皮生长因子受体突变的关系

Thyroid transcription factor-1 level is associated with epidermal growth factor receptor mutation status in patients with advanced lung adenocarcinoma

目的 分析晚期肺腺癌临床样本中甲状腺转录因子-1（TTF-1）表达水平及表皮生长因子受体（EGFR）的突变情况,探讨TTF-1作为EGFR突变状态潜在预测指标的可能性.方法 收集102例晚期肺腺癌患者血清和肿瘤组织样本,其中包含28例EGFR 19号外显子突变（19MT组）,23例EGFR 21号外显子突变（21 MT组）以及51例EGFR野生型（WT组）.分别使用酶联免疫吸附试验（ELISA）和免疫组织化学法分析血清和组织中TTF-1蛋白的表达水平.结果 19MT组和21MT组血清样本中TTF-1蛋白的表达水平高于WT组（分别为0.092、0.083和0.045 mg/L,F=27.653,P＜0.01）,3组的组织样本结果相同（19MT组、21MT组和WT组分别为0.682、0.644和0.441,F=47.665,P＜0.01）,而19MT组和21MT组TTF-1蛋白表达水平比较,差异无统计学意义（P＞0.05）.ELISA方法和IHC方法检测结果存在相关性（r=0.87,P＜0.01）.血清中TTF-1的表达水平与吸烟史相关（x2=4.639,P＜0.05）,与性别、年龄、肿瘤分期和转移无关（P＞0.05）.结论 血清中TTF-1的表达与EGFR突变具有相关性,提示TTF-1蛋白表达水平可作为EGFR突变状态的潜在预测指标.

Objective Epidermal growth factor receptor （EGFR） mutation status plays an important role in individual treatment of non-small cell lung cancer.However clinical tissue samples for mutation detection are not always available in advanced NSCLC.Thus an alternative method of EGFR mutation detection is required in NSCLC treatment.Recent studies have associated thyroid transcription factor 1 （TTF-1） with EGFR mutations in lung cancer.In this study,we detected expression of TTF-1 and EGFR mutations in 102 patients with advanced NSCLC and investigated the possibility of TTF-1 as a potential indicator of EGFR status.Methods Serum and tissue samples were collected from 102 patients with advanced NSCLC including 28 cases of EGFR mutation in 19 exon,23 cases of EGFR mutation in 21 exon and 51 cases of WT EGFR.Protein levels of TTF-1 in serum were quantified by enzyme-linked immunosorbent assay （ELISA）.Levels of TTF-1 in tissues were detected by immunohistochemistry （IHC）.SPSS 17 statistical software was used to analyze the data.Results In the serum the expression of TTF-1 in EGFR 19 and 21 exon MT groups both was higher than that in the WT group（19MT vs 21MT vs WT：0.092 vs 0.083 vs 0.045; F =27.653,P 〈 0.01）,and the result of the tissues was the same （19MT vs 21MT vs WT：0.682 vs 0.644 vs 0.441 ; F =47.665,P 〈 0.01）,but no differences between two MT groups were observed（P 〉 0.05）.The ELISA results and the IHC results were consistent （r =0.87,P 〈 0.01）.The expression of TTF-1 in serum showed a relationship with smoking history （x2 =4.639,P 〈 0.05）,but not with sex,age,TNM stage and metastasis （P 〉 0.05）.Conclusions These results indicated that TTF-1 expression was upregulated in EGFR mutated NSCLC compared to EGFR WT NSCLC.The level of TTF-1 maybe used as a potential marker of EGFR mutation status.