甲状腺转录因子1在肺腺癌患者中的表达及其与晚期肺腺癌预后的相关性

Expression of thyroid transcription factor 1 in patients with lung adenocarcinoma and its correlation with the prognosis of patients with advanced lung adenocarcinoma

目的分析甲状腺转录因子1(TTF-1)在肺腺癌患者中的表达情况,并探讨TTF-1表达与晚期肺腺癌患者预后的相关性。方法选取2012年1月至2016年6月西安市胸科医院786例确诊的肺腺癌患者,免疫组织化学法检测TTF-1的表达情况。分析TTF-1表达与患者临床病理特征及治疗、生存情况的关系,Cox风险比例模型分析TTF-1及临床病理特征与晚期肺腺癌患者预后的相关性。结果786例患者中,559例(71.12%)TTF-1阳性表达,227例(28.88%)TTF-1阴性表达。肿瘤分化程度高、分期早、无淋巴结和远处转移的患者TTF-1呈高表达,表达率分别为77.26%(197/255)、78.89%(269/341)、78.95%(225/285)、75.61%(372/492),与分化程度低、分期晚、有淋巴结和远处转移者的68.17%(362/531)、65.17%(290/445)、66.67%(334/501)、63.60%(187/294)比较,差异均有统计学意义(χ^2值分别为6.917、25.261、13.339、12.911,均P<0.05);TTF-1在原发病灶及转移病灶中的表达一致(κ=0.894,P<0.01)。385例无法手术的晚期肺腺癌患者中,TTF-1表达阳性患者的表皮生长因子受体(EGFR)突变比例(45.60%,109/239)高于阴性患者(26.02%,38/146),差异有统计学意义(χ^2=14.721,P<0.01);TTF-1表达阳性患者的中位无进展生存(PFS)时间较TTF-1表达阴性患者延长(6.00个月比4.20个月,P<0.01),无论EGFR是否突变TTF表达阳性患者中位PFS时间均较TTF-1表达阴性患者延长(P=0.003;P<0.01)。TTF-1表达(HR=0.793,95% CI 0.639~0.984,P=0.011)及EGFR基因状态(HR=0.694,95% CI 0.432~0.864,P=0.004)是晚期肺腺癌患者PFS的独立影响因素。结论TTF-1在肺腺癌中广泛表达,与肿瘤分化、分期、淋巴结转移及远处转移相关。TTF-1是晚期肺腺癌患者预后影响因素,可作为晚期肺腺癌患者预后的预测因子。

Objective To analysis the expression of thyroid transcription factor 1 (TTF-1) in patients with lung adenocarcinoma, and discuss the relationship between TTF-1 expression and prognosis of patients with advanced lung adenocarcinoma. Methods A total of 786 cases of lung adenocarcinoma who were admitted to Xi'an Chest Hospital from January 2012 to June 2016 were selected. The expression of TTF-1 was detected by immunohistochemistry. The relationship between TTF-1 expression and patients' clinicopathological features, treatment and survival were analyzed. Cox proportional hazard model was used to analyze the relationship between TTF-1 and prognosis of patients with advanced lung adenocarcinoma. Results Among 786 patients, 559 patients (71.12%) had positive TTF-1 expression, 227 patients (28.88%) had negative TTF-1 expression. The expression rates of TTF-1 in patients with well-differentiated, early stage, no lymph node metastasis, and no distant metastasis [77.26%(197/255), 78.89%(269/341), 78.95%(225/285), and 75.61%(372/492)] were higher than those in patients with poorly differentiated, late stage, lymph node metastasis and distant metastasis 68.17%(362/531), 65.17%(290/445), 66.67%(334/501), 63.60%(187/294), the differences were statistically significant (χ^2 values were 6.917, 25.261, 13.339, and 12.911, all P < 0.05). The expressions of TTF-1 in primary lesions and metastatic lesions were consistent (κ= 0.894, P < 0.01). Among 385 patients with advanced lung adenocarcinoma who were unable to perform the operation, the proportion of epidermal growth factor receptor (EGFR) mutation in TTF-1 positive expression patients (45.60%, 109/239) was significantly higher than that in TTF-1 negative expression patients (26.02%, 38/146), and the difference was statistically significant (χ^2= 14.721, P < 0.01). The median progression free survival (PFS) time of TTF-1 positive expression patients was significantly longer than that of TTF-1 negative expression patients (6.00 months vs. 4.20 months, P < 0.01), whether EGFR was mutation or not, the median PFS time of TTF-1 positive expression patients was significantly longer than that of TTF-1 negative expression patients (P= 0.003;P < 0.01). TTF-1 expression (HR= 0.793, 95% CI 0.639-0.984, P= 0.011) and EGFR gene status (HR=0.694, 95% CI 0.432-0.864, P= 0.004) were independent influencing factors affecting the PFS of patients with advanced lung adenocarcinoma. Conclusions TTF-1 is widely expressed in lung adenocarcinoma and is associated with tumor differentiation, staging, lymph metastasis and distant metastasis. TTF-1 is a prognostic influencing factor in patients with advanced lung adenocarcinoma and can be used as a predictor of treatment for patients with advanced lung adenocarcinoma.