School of Biomedical Engineering, Tianjin Medical University, Tianjin, 300070, China.
Curr Pharm Des. 2023;29(26):2091-2100. doi: 10.2174/1381612829666230901143203.
Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer with a poor prognosis and limited treatment options. Previous studies show that some components of the cholinergic pathway may play important roles in the tumorigenesis of lung cancer, including LUSC.
The purpose of this study is to investigate the involvement of cholinergic genes in immune infiltration in LUSC, and identify the key genes in the pathway and analyze their potential as targets for LUSC treatment and novel drugs.
We first screened the cholinergic genes associated with immune infiltration in LUSC based on transcriptomic samples and explored the correlation between the key genes and immune infiltrating cells and immune pathways. Then, we assessed the effect of immunotherapeutic response in the high and low-expression groups of key genes in vitro. And finally, we screened potential drugs for the treatment of LUSC.
We found that the expression of CHRNA6, the gene encoding the α6 subunit of nicotinic acetylcholine receptors (nAChR), was significantly correlated with the proportion of immune infiltrating cells in LUSC, and the high expression level of the gene was associated with poor prognosis of the disease. Also, the proportion of Tregs, M1 macrophages, and resting mast cells was correlated with the expression of CHRNA6. In addition, LUSC patients with higher CHRNA6 expression levels had better immunotherapy responses. Furthermore, we found that the drugs, i.e., adavosertib, varbulin and pyrazoloacridine, had a strong affinity with CHRNA6, with adavosertib binding most stably with the protein.
CHRNA6 may be associated with immune infiltration in LUSC and affects patient prognosis and immunotherapeutic response by regulating immune cells and immune pathways. In addition, adavosertib may be a potential drug for the treatment of LUSC.
肺鳞状细胞癌（LUSC）是一种预后较差且治疗选择有限的肺癌亚型。先前的研究表明，胆碱能途径的某些成分可能在肺癌的发生中发挥重要作用，包括 LUSC。
本研究旨在探讨胆碱能基因在 LUSC 免疫浸润中的作用，并确定该途径中的关键基因，分析其作为 LUSC 治疗和新型药物靶点的潜力。
我们首先基于转录组样本筛选与 LUSC 免疫浸润相关的胆碱能基因，并探讨关键基因与免疫浸润细胞和免疫途径的相关性。然后，我们评估了关键基因高表达和低表达组在体外的免疫治疗反应。最后，我们筛选了潜在的治疗 LUSC 的药物。
我们发现，编码烟碱型乙酰胆碱受体（nAChR）α6 亚单位的 CHRNA6 基因的表达与 LUSC 中免疫浸润细胞的比例显著相关，且该基因的高表达水平与疾病预后不良相关。此外，CHRNA6 的表达与 Tregs、M1 巨噬细胞和静止肥大细胞的比例相关。此外，LUSC 患者中 CHRNA6 表达水平较高者免疫治疗反应更好。此外，我们发现，药物，即 adavosertib、varbulin 和 pyrazoloacridine 与 CHRNA6 具有很强的亲和力，其中 adavosertib 与该蛋白的结合最稳定。
CHRNA6 可能与 LUSC 中的免疫浸润有关，并通过调节免疫细胞和免疫途径影响患者的预后和免疫治疗反应。此外，adavosertib 可能是治疗 LUSC 的潜在药物。
