缺少甲状腺转录因子1（TTF-1）与肺腺癌中表皮生长因子受体（EGFR）突变的频率较低有关。本研究的目的是评估TTF-1表达对晚期肺腺癌患者接受EGFR酪氨酸激酶抑制剂（TKI）治疗的临床反应的影响。回顾性分析在中国北京天坛医院和北京大学肿瘤医院于2009年4月至2023年5月期间收治的晚期肺腺癌患者的数据。共纳入227名被诊断为晚期肺腺癌的患者，其中28.2%（64/227）患有TTF-1阴性腺癌，而54.6%（124/227）携带EGFR突变。与TTF-1阳性相比，TTF-1阴性表达与男性性别（68.8% vs. 42.3%，p < 0.001）、重度吸烟史（57.8% vs. 36.2%，p = 0.003）、差分程度差（86.5% vs. 43.2%，p < 0.001）和较低的EGFR突变频率（26.6% vs. 65.6%，p < 0.001）显著相关。多变量逻辑回归分析显示低EGFR突变的流行（p < 0.001）和男性性别（p = 0.006）是TTF-1阴性表达的独立预测因素。相比于EGFR突变且TTF-1阳性的患者，缺乏TTF-1的患者在接受EGFR-TKI治疗后显示出更差的总体反应率（ORR；23.5% vs. 54.2%，p = 0.019）、疾病控制率（DCR；58.8% vs. 89.7%，p = 0.003）和中位进展无病生存期（PFS；2.9 vs. 11.6个月，p < 0.001）。具有TTF-1阴性和EGFR突变的肺腺癌患者对EGFR-TKI反应减弱。© 2023 作者。由中国肺癌医生集团和John Wiley & Sons Australia, Ltd.出版的《胸部肿瘤》发表。

The absence of thyroid transcription factor 1 (TTF-1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF-1 expression on the clinical response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD.The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed.A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF-1-negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF-1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF-1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF-1. Patients lacking TTF-1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression-free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR-TKIs compared to the TTF-1-positive patients with EGFR mutations.Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.