Exploring the role and mechanism of rheumatoid arthritis-related pathway in squamous lung cancer based on Mendelian randomization analysis

Abstract

Objective：Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory joint disease. Squamous cell carcinoma of the lung (LUSC) is a malignant tumor of non-small cell lung cancer. Studies have shown a complex relationship between rheumatoid arthritis and lung cancer. This study aimed to investigate the role and mechanism of rheumatoid arthritis-related pathways in lung squamous carcinoma using bioinformatics methods combined with Mendelian randomization analysis. Methods: Download RA gene expression profile data set GSE1919 from GEO database, screen differential genes using GEO 2 R tool, and download lung gene expression profile data from TCGA database, and screen differential genes by Rstudio software. GO / KEGG functional enrichment analysis yielded RA signaling pathway genes. After downloading RA signaling pathway SNP data as exposure factor and lung SNP data for squamous cell carcinoma as outcome factor, we used two-sample Mendelian randomization analysis to determine the causal relationship between RA signaling pathway and lung squamous cell carcinoma. In addition, gene-drug regulatory network, ceRNA regulatory network, immune cell infiltration analysis and validation group difference analysis were constructed. Results: We found 188 genes codifferentially expressed between RA and LUSC. Results of GO / KEGG functional enrichment analysis showed that these differential genes were mainly enriched in the rheumatoid arthritis signaling pathway. The results of Mendelian randomization analysis showed that enhanced activity of RA signaling pathway was associated with a reduced risk of lung squamous carcinoma. Conclusion: The study found that the enhanced activity of rheumatoid arthritis signaling pathway may be associated with the reduced risk of breast cancer, which provides new ideas and vision for studying the mechanism and treatment of lung squamous cell carcinoma.