Li Yinan, Wang Wenting, Wang Yaoyao, Zhou Ce, Zou Xin, Wang Yixuan, Wang Ning
Department of Respiratory and Critical Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Department of Oncology, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
Transl Cancer Res. 2025 Jul 30;14(7):4293-4304. doi: 10.21037/tcr-2024-2587. Epub 2025 Jun 19.
Nicotine, the principal addictive component of tobacco smoke, promotes lung cancer cell proliferation via α7 nicotinic acetylcholine receptors (α7-nAChRs). Programmed death-ligand 1 (PD-L1) serves as a crucial predictive biomarker for immune checkpoint inhibitor (ICI) therapy in lung squamous cell carcinoma (LUSC). This study aimed to investigate the expression patterns of α7-nAChR and its encoding gene in LUSC tissues, and to evaluate their associations with PD-L1 expression.
expression, its correlation with clinicopathological features, and survival outcomes in LUSC were analyzed using The Cancer Genome Atlas (TCGA) database and Kaplan-Meier plotter. The expression levels of α7-nAChR and PD-L1 in LUSC tissues and cell lines were evaluated by immunohistochemistry and Western blot (WB). Following nicotine stimulation and small interfering RNA (siRNA) transfection, messenger RNA (mRNA) expression levels of , signal transducer and activator of transcription 3 (STAT3), and CD274 (PD-L1) were quantified using quantitative real-time polymerase chain reaction (qRT-PCR), while their protein levels were assessed by WB.
expression was significantly elevated in LUSC tissues and cell lines compared to adjacent normal tissues and bronchial epithelial cell lines (P<0.05), and correlated with smoking status. Higher expression was associated with shorter overall survival. Nicotine stimulation (1.0 μM) significantly increased the mRNA expression levels of , STAT3, and CD274 in LUSC cell lines. Knockdown of siRNA-mediated in LUSC cell lines decreased STAT3 phosphorylation (pSTAT3) and PD-L1 protein levels, while attenuating nicotine-induced PD-L1 upregulation. STAT3 silencing had no significant effect on α7-nAChR protein expression but downregulated PD-L1 protein levels and attenuated nicotine-induced PD-L1 upregulation.
α7-nAChR and its encoding gene are upregulated in LUSC tissue and are associated with smoking status. Patients with high expression of have a relatively worse prognosis. Nicotine may upregulate PD-L1 expression in LUSC through the α7-nAChR/STAT3 pathway.
尼古丁是烟草烟雾中的主要成瘾成分，通过α7烟碱型乙酰胆碱受体（α7-nAChRs）促进肺癌细胞增殖。程序性死亡配体1（PD-L1）是肺鳞状细胞癌（LUSC）免疫检查点抑制剂（ICI）治疗的关键预测生物标志物。本研究旨在调查α7-nAChR及其编码基因在LUSC组织中的表达模式，并评估它们与PD-L1表达的相关性。
使用癌症基因组图谱（TCGA）数据库和Kaplan-Meier绘图仪分析LUSC中α7-nAChR的表达、其与临床病理特征的相关性以及生存结果。通过免疫组织化学和蛋白质印迹（WB）评估LUSC组织和细胞系中α7-nAChR和PD-L1的表达水平。在尼古丁刺激和小干扰RNA（siRNA）转染后，使用定量实时聚合酶链反应（qRT-PCR）定量α7-nAChR、信号转导和转录激活因子3（STAT3）和CD274（PD-L1）的信使核糖核酸（mRNA）表达水平，同时通过WB评估它们的蛋白质水平。
与相邻正常组织和支气管上皮细胞系相比，LUSC组织和细胞系中α7-nAChR的表达显著升高（P<0.05），且与吸烟状态相关。较高的α7-nAChR表达与较短的总生存期相关。尼古丁刺激（1.0 μM）显著增加了LUSC细胞系中α7-nAChR、STAT3和CD274的mRNA表达水平。在LUSC细胞系中敲低siRNA介导的α7-nAChR可降低STAT3磷酸化（pSTAT3）和PD-L1蛋白水平，同时减弱尼古丁诱导的PD-L1上调。STAT3沉默对α7-nAChR蛋白表达无显著影响，但下调了PD-L1蛋白水平并减弱了尼古丁诱导的PD-L1上调。
α7-nAChR及其编码基因在LUSC组织中上调，且与吸烟状态相关。α7-nAChR高表达的患者预后相对较差。尼古丁可能通过α7-nAChR/STAT3途径上调LUSC中PD-L1的表达。
