Identification of key biomarkers in steroid-induced osteonecrosis of the femoral head and their correlation with immune infiltration by bioinformatics analysis

Jun Zhao,Xingshi Zhang,Junjie Guan,Jizhao Jiang,Yu Su

doi:10.1186/s12891-022-04994-7

Abstract

ObjectiveThis study aimed to identify key diagnostic markers and immune infiltration of (SONFH) by bioinformatics analysis.MethodsRelated SONFH datasets were downloaded from the Gene Expression Omnibus (GEO) database. First, we identified the differentially expressed genes (DEGs) and performed the functional enrichment analysis. Then weighted correlation network analysis (WGCNA) and the MCODE plug-in in Cytoscape were used to identify the diagnostic markers of SONFH. Finally, CIBERSORT was used to analyze the immune infiltration between SONFH and healthy controls, and the correlation between infiltrating immune cells and diagnostic markers was analyzed.ResultsTYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be key diagnostic markers of SONFH. Immune cell infiltration analysis revealed that Memory B cells and activated dendritic cells may be related to the SONFH process. Moreover, HCK was negatively correlated with CD8 T cells, and neutrophils were positively correlated with those key diagnostic markers.ConclusionsTYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be used as diagnostic markers of SONFH, and immune-related mechanism of SONFH and the potential immunotherapy are worthy of further study.

Highlights

Osteonecrosis of the femoral head (ONFH) is a debilitating clinical disease characterized by the progressive necrosis of the bone marrow and bone cells, and most patients eventually develop progressive femoral head collapse and degenerative arthritis [1]
Analysis of correlation between key diagnostic markers and immune infiltrating cells The results of Spearman correlation analysis (Table S8) revealed that HCK was negatively correlated with CD8 T cells (r = − 0.541, p = 0.043) and neutrophils were positively correlated with TYROBP (r = 0.549, p = 0.035), TLR2 (r = 0.689, p = 1.25e-04), P2RY13 (r = 0.731, p = 1.27e-05), TLR8 (r = 0.676, p = 2.38e-04), HCK (r = 0.712, p = 3.71e-05), MNDA (r = 0.706, p = 5.11e-05), and NCF2 (r = 0.768, p = 1.08e-06) (Fig. 7A)
We used CIBERSORT to evaluate SONFH immune infiltration and found that the decreased infiltration of memory B cells and activated dendritic cells may be related to the occurrence and development of SONFH

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) is a debilitating clinical disease characterized by the progressive necrosis of the bone marrow and bone cells, and most patients eventually develop progressive femoral head collapse and degenerative arthritis [1]. The etiology of ONFH remains unclear [2], many studies have. The specific pathogenesis of SONFH remains unclear, but recent studies have revealed that immune cell infiltration associate with its occurrence and development. Studies demonstrated that the frequency of activated B cells in peripheral blood of SONFH was higher than healthy controls, and the degree of the femoral head collapse was positively correlated with the percentage of CD86 + CD19 + B cells [7]. Ma et al [5] found that immunomodulatory cells, especially inhibitory T lymphocytes, which mainly regulate the bone mass balance of the femoral head by secreting a variety of cytokines such as osteoprotegerin and interleukin-4, are strictly related to the pathogenesis of nontraumatic ONFH. From the view of the immune system, evaluating the differences in the composition of immune infiltrating cells in SONFH is of great value to elucidating its molecular mechanism and identifying molecular markers related to immune infiltration

Methods

Results

Discussion

Conclusion