Objective: Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified.

Methods: Gene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein–protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280.

Results: Five datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: TRIM22, IFI6, IFITM1, IFI35, and IRF9.

Conclusions: Our bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.