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.