背景:甲状腺转录因子1(TTF-1)的缺失与肺腺癌(LUAD)中表皮生长因子受体(EGFR)突变频率较低有关。这项研究的目的是评估TTF-1表达对晚期LUAD患者对EGFR-酪氨酸激酶抑制剂(TKI)治疗的临床反应的影响。
方法:对2009年4月至2023年5月北京天坛医院和北京大学肿瘤医院收治的晚期LUAD患者资料进行回顾性分析。
结果:共纳入227例诊断为晚期LUAD的患者,其中28.2%(64/227)为TTF-1阴性腺癌,54.6%(124/227)存在EGFR突变。TTF-1阴性表达与男性显著相关(68.8%vs.42.3%,p<0.001),大量吸烟史(57.8%vs.36.2%,p=0.003),低分化肿瘤(86.5%vs.43.2%,p<0.001),EGFR突变的频率较低(26.6%vs.65.6%,p<0.001)与TTF-1阳性相比。多因素Logistic回归分析显示,EGFR突变发生率低(p<0.001)和男性(p=0.006)是TTF-1阴性表达的独立预测因素。缺乏TTF-1的患者的总体反应率也较差(ORR;23.5%vs.54.2%,p=0.019),疾病控制率(DCR;58.8%vs.89.7%,p=0.003),和中位无进展生存期(PFS;2.9vs.11.6个月,与具有EGFR突变的TTF-1阳性患者相比,用EGFR-TKIs治疗后p<0.001)。
结论:TTF-1阴性和EGFR突变型LUAD患者对EGFR-TKIs的反应减弱。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.