Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head

Abstract

ABSTRACT Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive disease that leads to an increased disability rate. This study aimed to ascertain biomarkers, infiltrating immune cells, and therapeutic drugs for SONFH. The gene expression profile of the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the NetworkAnalyst platform. Functional enrichment, protein-protein interaction network (PPI), and module analyses were performed using Metascape tools. An immune cell abundance identifier was used to explore immune cell infiltration. Furthermore, hub genes were identified based on maximal clique centrality (MCC) evaluation using cytoHubba application and confirmed by qRT-PCR using clinical samples. Finally, the L1000 platform was used to determine potential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effects of aspirin. In total, 429 DEGs were identified in SONFH samples. Functional enrichment analysis showed that these DEGs were enriched in myeloid leukocyte activation and osteoclast differentiation processes. A set of nine immune cell types was confirmed to be markedly different between the SONFH and control samples. All 10 hub genes were significantly highly expressed in the serum of SONFH patients, as shown by qRT-PCR. Finally, the therapeutic effect of aspirin on SONFH was examined in animal experiments. Taken together, our data revealed the hub genes and infiltrating immune cells in SONFH, and we also screened potential drugs for use in SONFH treatment.