Title:Involvement of CHRNA6 in the Immune Response in Lung Squamous Cell
Carcinoma and its Potential as a Drug Target for the Disease
Volume: 29
Issue: 26
Author(s): Fengyu Zhang, Meidi Zhang, Xin Yuan, Yulian Tao and Ju Wang*
Affiliation:
- School of Biomedical Engineering, Tianjin Medical University, Tianjin, 300070, China
Keywords:
Cholinergic system, CHRNA6, lung squamous cell carcinoma, immune infiltration, immunotherapy, drug screening.
Abstract:
Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
