Abstract
Lung cancer and asthma are both global health problems with significant economic consequences. Recent studies have demonstrated that asthma may be a risk factor for lung cancer. The present study aimed to explore the pathogenesis between these two diseases through a comprehensive analysis. Differentially expressed genes (DEGs) screened in the asthma-related GSE165934 dataset were analyzed to find relevant inflammatory pathways. Overlapping genes regulated by inflammatory pathways and lung cancer-DEGs from The Cancer Genome Atlas (TCGA) were obtained and subjected to survival and gene-wide mutation analyses, and nomogram construction to determine the hub gene. The hub gene was further analyzed through expression validation, immunoassays and functional experiments to investigate its role and mechanism in lung cancer. Functional enrichment analysis showed that 1,275 DEGs from GSE165934 were closely associated with the Toll-like receptor signaling pathway, and 8 overlapping genes were identified from 12 genes regulated by the Toll-like receptor signaling pathway and 3,134 TCGA-DEGs. After a series of bioinformatics analyses, it was found that triggering receptor expressed on myeloid cells 1 (TREM1) was the hub gene involved in the mechanism of asthma and lung cancer. TREM1 was also found to be a suppressor gene in lung cancer correlated with immune cells, immune checkpoint-related genes and tumor mutational burden score. Additionally, the results of Cell Counting Kit-8 and Transwell experiments demonstrated that overexpression of TREM1 could significantly inhibit the invasion, proliferation and migration of lung cancer cells. Reverse transcription-quantitative PCR and western blotting demonstrated that the overexpression of TREM1 could also significantly reduce the level of Toll-like receptor signaling pathway proteins. The present findings suggest that TREM1 is associated with the mechanism of asthma and lung cancer through its regulation of the Toll-like receptor signaling pathway. Furthermore, TREM1 may serve as a potential treatment target and prognostic indicator for patients with lung cancer.