Identification of immune-related genes and serum miR-100-5p in idiopathic inflammatory myopathy-related heart failure by integrated bioinformatics analysis and clinical validation

OBJECTIVE: Idiopathic inflammatory myopathy (IIM) is a collection of autoimmune disorders marked by muscle inflammation, with heart failure (HF) being a common and deadly complication. Exploring the underlying mechanisms and diagnostic markers for HF in IIM has significant clinical value. METHODS: We identified shared differentially expressed genes (DEGs) between HF and IIM using transcriptome data from the Gene Expression Omnibus (GEO). DEGs underwent functional enrichment analysis via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Key genes were screened using two machine-learning algorithms and a protein-protein interaction network. Immune cell infiltration was estimated using the CIBERSORT algorithm, and its correlation with key genes was assessed. The key gene-related regulatory transcription factors (TFs) and miRNAs were predicted using miRNet, followed by validation through both online datasets and clinical samples. RESULTS: Seventy DEGs were shared by IIM and HF, primarily involved in immune and inflammatory responses. Key genes, including DDX60, CCL5, and IFIT3, exhibited strong diagnostic potential in both IIM and HF cohorts. Expression of IFIT3 and CCL5 was negatively associated with Tregs. In order to uncover the control of important genes, we also constructed TF-gene and miRNA-gene networks. Lastly, we confirmed that IIM with HF had higher levels of miR-100-5p expression than those without HF. CONCLUSION: DDX60, CCL5, and IFIT3 are likely central to the development of HF in IIM. Additionally, serum levels of miR-100-5p may serve as a potential biomarker for detecting HF in IIM patients.