Background/Objectives:Despite advances in immunotherapy, reliable biomarkers beyond PD-L1 expression are urgently needed to optimize treatment decisions in advanced non-squamous NSCLC. Thyroid Transcription Factor-1 (TTF-1), a biomarker associated with favorable prognosis in chemotherapy-treated patients, has unclear prognostic implications in the immunotherapy era.Methods: We conducted a multicenter retrospective study involving 163 advanced non-squamous NSCLC patients treated with first-line immunotherapy or chemo-immunotherapy and an additional historical chemotherapy-only cohort (n = 37). We evaluated the prognostic significance of TTF-1 expression for progression-free survival (PFS) and overall survival (OS). A systematic review and meta-analysis, performed following PRISMA guidelines, integrated our findings with existing evidence. Hazard ratios (HRs) were calculated using Cox proportional hazards models.Results: TTF-1 negativity was associated with significantly worse median PFS (6.7 vs. 16 months; HR 2.22, 95% CI 1.59–3.13;p< 0.001) and OS (11.5 vs. 26.4 months; HR 2.33, 95% CI 1.64–3.45;p< 0.001) compared to TTF-1 positivity. The prognostic value of TTF-1 was independent of PD-L1 status, with limited predictive relevance of PD-L1 expression observed within TTF-1-negative tumors. Meta-analysis (9 studies, 14 cohorts, n = 2019 patients) confirmed significantly inferior outcomes for TTF-1-negative patients across multiple immunotherapy-based regimens (pooled HR for PFS: 1.75, 95% CI 1.50–2.04; OS: 1.76, 95% CI 1.45–2.14).Conclusions: TTF-1 negativity independently predicts poor prognosis in advanced non-squamous NSCLC treated with immunotherapy-based regimens, identifying patients with limited benefit despite high PD-L1 expression. Integrating TTF-1 status into clinical practice may guide personalized treatment strategies, highlighting the need for prospective validation.
**背景/目的：** 尽管免疫治疗取得进展，但除PD-L1表达外，仍需寻找可靠的生物标志物以优化晚期非鳞状非小细胞肺癌的治疗决策。甲状腺转录因子-1（TTF-1）在化疗患者中是与良好预后相关的生物标志物，但其在免疫治疗时代的预后意义尚不明确。 **方法：** 我们开展了一项多中心回顾性研究，纳入163例接受一线免疫治疗或免疫联合化疗的晚期非鳞状非小细胞肺癌患者，并增加了一个历史性单纯化疗队列（n=37）。我们评估了TTF-1表达对无进展生存期（PFS）和总生存期（OS）的预后意义。同时，遵循PRISMA指南进行了系统综述和荟萃分析，将我们的发现与现有证据整合。使用Cox比例风险模型计算风险比（HR）。 **结果：** 与TTF-1阳性相比，TTF-1阴性患者的中位PFS（6.7个月 vs. 16个月；HR 2.22，95% CI 1.59–3.13；p < 0.001）和OS（11.5个月 vs. 26.4个月；HR 2.33，95% CI 1.64–3.45；p < 0.001）均显著更差。TTF-1的预后价值独立于PD-L1状态，且在TTF-1阴性肿瘤中观察到PD-L1表达的预测相关性有限。荟萃分析（9项研究，14个队列，n=2019例患者）证实，在接受多种免疫治疗方案的TTF-1阴性患者中，结局均显著更差（PFS合并HR：1.75，95% CI 1.50–2.04；OS合并HR：1.76，95% CI 1.45–2.14）。 **结论：** TTF-1阴性可独立预测接受免疫治疗方案治疗的晚期非鳞状非小细胞肺癌患者的不良预后，识别出即使PD-L1高表达也获益有限的患者。将TTF-1状态整合到临床实践中可能有助于指导个体化治疗策略，并凸显了进行前瞻性验证的必要性。
肿瘤(癌症)患者之家