Identification of immune-related genes in diagnosing atherosclerosis with rheumatoid arthritis through bioinformatics analysis and machine learning

Abstract

Background: Increasing evidence has proven that rheumatoid arthritis (RA) can aggravate atherosclerosis (AS), and we aimed to explore potential diagnostic genes for patients with AS and RA.

Methods: We obtained the data from public databases, including Gene Expression Omnibus (GEO) and STRING, and obtained the differentially expressed genes (DEGs) and module genes with Limma and weighted gene co-expression network analysis (WGCNA). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis, the protein-protein interaction (PPI) network, and machine learning algorithms [least absolute shrinkage and selection operator (LASSO) regression and random forest] were performed to explore the immune-related hub genes. We used a nomogram and receiver operating characteristic (ROC) curve to assess the diagnostic efficacy, which has been validated with GSE55235 and GSE73754. Finally, immune infiltration was developed in AS.

Results: The AS dataset included 5,322 DEGs, while there were 1,439 DEGs and 206 module genes in RA. The intersection of DEGs for AS and crucial genes for RA was 53, which were involved in immunity. After the PPI network and machine learning construction, six hub genes were used for the construction of a nomogram and for diagnostic efficacy assessment, which showed great diagnostic value (area under the curve from 0.723 to 1). Immune infiltration also revealed the disorder of immunocytes.

Conclusion: Six immune-related hub genes (NFIL3, EED, GRK2, MAP3K11, RMI1, and TPST1) were recognized, and the nomogram was developed for AS with RA diagnosis.

Keywords: atherosclerosis; diagnosis; immune infiltration; machine learning; rheumatoid arthritis.