Identification and molecular mechanism study of hallmark genes associated with steroidinduced osteonecrosis of the femoral head

Abstract

Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe disease. Nonetheless, the pathogenesis of SONFH is not fully understood, and it is challenging to make an early diagnosis. This study aimed to explore the hallmark genes associated with SONFH and predict potential biomarkers for SONFH. The microarray dataset GSE123568 was obtained from the Gene Expression Omnibus (GEO) database. The Weighted Gene Co-expression Network Analysis (WGCNA) and limma R-package were used to screen the intersection genes between the interest module genes and differential expression genes (DEGs). A protein-protein interaction (PPI) network, cross-talk, and receiver operating characteristic (ROC) curve were utilized to identify the optimal hallmark genes. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis (GSEA) were performed to explore the potential molecular mechanism of genes. The single-sample Gene Set Enrichment Analysis (ssGSEA) and CIBERSORT algorithm were used to analyze the immune infiltration level in SONFH. There were 96 intersection genes acquired between the interest module and DEGs. Based on the PPI network, cross-talk, and ROC curve analysis, we identified 6 SONFH-related hallmark genes, including TYROBP, TLR8, TLR2, LILRB2, HCK, and TREM1, which showed heterogeneous biological functions or molecular mechanisms. The Toll-like receptor (TLR) signaling pathway was considered the primary pathway in the development of SONFH. Finally, we found that the neutrophils might be the culprit in the SONFH. Our study identified some SONFH-related hallmark genes and revealed novel insights into the biological mechanism of SONFH, which provided a theoretical foundation for further experimental study and contributed to understanding the pathogenesis of SONFH.