Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis

Abstract

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.

Screening and validation of differentially expressed genes in polymyositis

“…This duality in function extends to their participation in antiviral immunity and the regulation of cellular proliferation and immune activity [ 14 ]. Our findings are in alignment with Si Chen et al's analysis, which also identified IRF9 and hub genes within the IFN pathway, such as TRIM22, IFI6, IFITM1, and IFI35, as noteworthy players in PM pathogenesis [ 15 ]. Additionally, Tournadre A and colleagues observed that IFN-I secretion led to an upsurge in HLA-I gene expression [ 16 ].…”

Idiopathic inflammatory myopathies: one year in review 2022

“…Interestingly, all these genes are involved in the immune response to virus infections and the type I interferon (IFN) signalling pathway. Chen et al confirmed the role of IFI16 as a putative hub gene in DM and polymyositis (PM) and identified four other putative hubs (TRIM22, IFITM1, IFI35, and IRF9) (4). Similar results were found in studies looking for IBM marker genes (5).…”

“…Idiopathic inflammatory myopathies: one year in review 2022 E. Dourado 1 , F. Bottazzi 2,3 , C. Cardelli 4,5 , E. Conticini 6 , J. Schmidt 7 , L. Cavagna 2,3 , S. Barsotti 4,8 Idiopathic inflammatory myopathies: one year in review 2022 / E. Dourado et al…”

Mitochondrial-related hub genes in dermatomyositis: muscle and skin datasets-based identification and in vivo validation

“…Furthermore, LAP3 contributes to the depletion of arginine induced by IFN-γ in a bovine mammary epithelial cell model ( Li et al, 2022 ). While only one study has identified an upregulation in LAP3 expression within DM ( Chen et al, 2022 ), the exact underlying mechanism remains to be elucidated. In DM, a disease with significant mitochondrial dysfunction, patients exhibit a notable reduction in aerobic capacity with histopathological and biochemical evidence supporting the presence of OXPHOS dysfunction, particularly in the perifascicular regions ( Woo et al, 1988a ; Cea et al, 2002 ; Alhatou et al, 2004 ; Varadhachary et al, 2010 ; Meyer et al, 2017 ).…”