Identification of hub genes and therapeutic drugs in osteonecrosis of the femoral head through integrated bioinformatics analysis and literature mining

Abstract

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease leading to severely limited function. By far, the etiology and pathogenesis of ONFH are not fully understood, and surgery is the only effective way to treat ONFH. This study aims to identify hub genes and therapeutic drugs in ONFH. Two gene expression profiles were downloaded from the gene expression omnibus database, and the hub genes and candidate drugs for ONFH were identified through integrated bioinformatics analysis and cross-validated by literature mining. A total of 159 DEGs were identified. PTGS2, LRRK2, ANXA5, IGF1R, MCL1, TIMP2, LYN, CD68, CBL, and RUNX2 were validated as 10 hub genes, which has considerable implications for future genetic research and related research fields of ONFH. Our findings indicate that 85 drugs interact with ONFH, with most drugs exhibiting a positive impact on ONFH by promoting osteogenesis and angiogenesis or inhibiting microcirculation embolism, rather than being anti-inflammatory. Our study provides novel insights into the pathogenesis, prevention, and treatment of ONFH.

Figure 1

Differentially expressed genes (DEGs) in ONFH patients. The volcano plots were constructed based on (A) GSE123568, and (B) GSE74089. The green points indicated the down-regulated DEGs, the red points indicated the up-regulated DEGs, and the black points indicated genes with no significant differences under the cutoff criteria: adjusted P-value < 0.05 and | log2^FC |> 1. (C) Venn diagram showed the overlap of DEGs in 2 datasets.

Figure 2

Bubble map for GO and KEGG pathway analyses of DEGs. The top 10 or all (if less than 10) significant items of the GO and KEGG pathway enrichment analysis were illustrated in (A) biological process, (B) cellular components, (C) molecular function, and (D) KEGG pathways. P < 0.05 was considered statistically significant.

Figure 3

PPI network of 159 DEGs. Disconnected nodes had been hidden in the network.

Figure 4

PPI network and ROC curves of the hub genes. (A) The PPI network of the hub genes with each other. The closer to red, the higher the Degree score. (B) The PPI network of the hub genes and interacting genes. Disconnected nodes had been hidden in the network. The ROC curves of (C) PTGS2, (D) LRRK2, (E) ANXA5, (F) IGF1R, (G) MCL1, (H) TIMP2, (I) LYN, (J) CD68, (K) CBL, and (L) RUNX2.

Figure 5

The drug-gene interactions network Constructed in Cytoscape. Yellow points represented genes and green points represented drugs. The thicker the connective line, the more the evidence.