Bioinformatics Analysis of Gene Expression Profiles of Immune-mediated Necrotizing Myopathy

Abstract

Background: Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy with limited therapeutic measures. This study aims to elucidate the potential biomarkers and investigate the underlying mechanisms in IMNM. Materials and Methods: Microarray datasets in GSE128470 and GSE39454 were obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were filtrated by limma package in R statistical software. Functional enrichment analyses were performed using DAVID online tools. STRING database was used to construct protein‑protein interaction (PPI) networks. The module analysis and hub genes validation were performed using Cytoscape software. Results: Integrated analysis of two databases revealed 160 co-expressed DEGs in IMNM, including 80 downregulated genes and 80 upregulated genes. GO enrichment analysis revealed that sarcomere is the most significantly enriched GO term within the DEGs. KEGG pathway enrichment analysis revealed significant enrichment pathways in cancer. A PPI network consisting of 115 nodes and 205 edges were constructed and top 20 hub genes were identified. Two key modules from the network were identified. Eight hub genes in module 1 (MYH3, MYH7B, MYH8, MYL5, MYBPH, ACTC1, YNNT 2 and MYOG) are tightly associated with skeletal muscle construction. Seven hub genes in module 2 (C1QA, TYROBP, MS4A6A, RNASE6, FCGR2A, FCER1G and LAPTM5) mainly take part in immune response. Conclusions: Our research indicated that cancer-related pathways, skeletal muscle construction pathways and immune-mediated pathways might participate in the development of IMNM. Identified hub genes may serve as potential biomarkers or targets for early diagnosis.