Analyzing the Involvement of Cholinesterases in the Immune Landscape of Lung Adenocarcinoma and Their Prognostic Values

Abstract

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and its prognosis is poor. The cholinergic system is involved in the development of lung cancer but its role is still unclear. In this study, we collected 231 cholinergic-related genes, and examined their expression in LUAD samples and normal tissues, from which 37 differentially expressed genes were screened. Then, by survival analysis, we identified 7 genes related to the prognosis of LUAD, among which acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) were included. The expression of AChE was upregulated in LUAD samples, and its expression had a significant positive correlation with the prognosis of male patients. But the expression of BChE was down-regulated in LUAD samples, and the elevated BChE expression was associated with a good prognosis in women and non-smoking patients. We also observed a close relationship between the two genes and immune landscape of LUAD. The AChE high expression patients had a higher ratio of tumor-infiltrating immune cells than the low expression patients, while the BChE high expression group had higher ratios of both tumor-infiltrating immune cells and stromal cells. We collected a total of 113 immunomodulatory genes associated with AChE and BChE to build an immunoregulatory network, which comprised several gene clusters. We also found that the expression of AChE and BChE was associated with immune escape in LUAD. Our results showed that AChE and BChE may play an important role in the development of LUAD, and could be promising biomarkers and targets for its diagnosis and treatment.