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首页> 外文期刊>Journal of Thoracic Disease >Correlation between thyroid transcription factor-1 expression, immune-related thyroid dysfunction, and efficacy of anti-programmed cell death protein-1 treatment in non-small cell lung cancer
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Correlation between thyroid transcription factor-1 expression, immune-related thyroid dysfunction, and efficacy of anti-programmed cell death protein-1 treatment in non-small cell lung cancer

机译：非小细胞肺癌中甲状腺转录因子-1表达，免疫相关性甲状腺功能障碍与抗程序性细胞死亡蛋白-1治疗疗效的相关性

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Background: Recent studies have suggested a correlation between immune-related thyroid dysfunction (irTD) and the superior efficacy of anti-programmed cell death protein-1 (anti-PD-1) treatment in non-small cell lung cancer (NSCLC). Embryologically, the lung and thyroid are similar in origin, and thyroid transcription factor-1 (TTF-1) expresses in both organs, including NSCLC. We explored our hypothesis that TTF-1 expression in NSCLC might correlate with irTD incidence and anti-PD-1 treatment efficacy. Methods: We identified 132 patients with NSCLC treated with anti-PD-1 antibody at our hospital between December 2015 and June 2017. We evaluated TTF-1 expression in tumor by immunohistochemistry using a mouse monoclonal antibody (clone 8G7G3/1, 1:100, Dako). IrTD was defined as two or more successive abnormal levels of thyroid-stimulating hormone (TSH) during anti-PD-1 treatment. We retrospectively assessed correlations between TTF-1 expression in tumor, irTD incidence, and anti-PD-1 treatment efficacy. Results: Of 132 patients, 67 (51%) and 65 (49%) were positive and negative for TTF-1, respectively. We observed irTD in 19 patients (6 positives and 13 negatives for TTF-1). The incidence of irTD was 9% and 20% in TTF-1-positive and TTF-1-negative NSCLCs, respectively (P=0.086). Particularly, in non-squamous (NSQ) cell carcinomas, the irTD incidence was significantly higher in patients negative for TTF-1 (30%) than in those positive for TTF-1 (9%; P=0.010), and TTF-1 expression was identified as a significant risk factor for irTD on multivariate logistic regression analysis [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.05–0.59; P=0.005]. Furthermore, longer median progression-free survival (10.3 months) was observed in patients with TTF-1-negative NSCLC with irTD compared to those with TTF-1-positive NSCLC with irTD, TTF-1-positive NSCLC without irTD, and TTF-1-negative NSCLC without irTD (4.2, 1.4, and 2.4 months, respectively). Conclusions: TTF-1 expression in NSCLC might correlate with irTD and anti-PD-1 treatment efficacy.
机译：背景：最近的研究表明，免疫相关的甲状腺功能不全（irTD）与抗编程性细胞死亡蛋白1（anti-PD-1）在非小细胞肺癌（NSCLC）中的优异疗效之间存在相关性。在胚胎学上，肺和甲状腺的起源相似，并且甲状腺转录因子-1（TTF-1）在包括NSCLC在内的两个器官中表达。我们探索了这样的假设，即NSCLC中TTF-1表达可能与irTD发生率和抗PD-1治疗功效相关。方法：我们在2015年12月至2017年6月期间在我院鉴定了132例接受抗PD-1抗体治疗的NSCLC患者。我们使用小鼠单克隆抗体（克隆8G7G3 / 1，1：100）通过免疫组化评估了TTF-1在肿瘤中的表达，达科）。 IrTD被定义为抗PD-1治疗期间两个或两个以上连续的甲状腺刺激激素（TSH）异常水平。我们回顾性评估了肿瘤中TTF-1表达，irTD发生率和抗PD-1治疗功效之间的相关性。结果：在132例患者中，TTF-1阳性和阴性分别为67名（51％）和65名（49％）。我们在19例患者中观察到irTD（TTF-1阳性6例，阴性13例）。在TTF-1阳性和TTF-1阴性的NSCLC中，irTD的发生率分别为9％和20％（P = 0.086）。特别是，在非鳞状（NSQ）细胞癌中，TTF-1阴性的患者（30％）的irTD发生率显着高于TTF-1阳性的患者（9％; P = 0.010）和TTF-1在多元逻辑回归分析中，表达被确定为irTD的重要危险因素[比值比（OR）为0.18; 95％置信区间（CI），0.05-0.59; P = 0.005]。此外，与患有irTD的TTF-1阳性NSCLC，没有irTD的TTF-1阳性NSCLC和没有TF的TTF-1阳性NSCLC相比，患有irTD的TTF-1阴性NSCLC患者的中位无进展生存期更长（10.3个月）。无irTD的1阴性NSCLC（分别为4.2、1.4和2.4个月）。结论：NSCLC中TTF-1的表达可能与irTD和抗PD-1的疗效有关。

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