HEMGN和SLC2A1可能是激素性股骨头坏死的潜在诊断生物标志物：基于WGCNA和差异表达基因筛选的研究
HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening.
作者信息
Wu Zhixin, Wen Yinxian, Fan Guanlan, He Hangyuan, Zhou Siqi, Chen Liaobin
机构信息
Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan City, 430071, Hubei Province, China.
Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
出版信息
BMC Musculoskelet Disord. 2021 Jan 15;22(1):85. doi: 10.1186/s12891-021-03958-7.
BACKGROUND
Steroid-induced osteonecrosis of the femoral head (SONFH) is a chronic and crippling bone disease. This study aims to reveal novel diagnostic biomarkers of SONFH.
METHODS
The GSE123568 dataset based on peripheral blood samples from 10 healthy individuals and 30 SONFH patients was used for weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. The genes in the module related to SONFH and the DEGs were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Genes with |gene significance| > 0.7 and |module membership| > 0.8 were selected as hub genes in modules. The DEGs with the degree of connectivity ≥5 were chosen as hub genes in DEGs. Subsequently, the overlapping genes of hub genes in modules and hub genes in DEGs were selected as key genes for SONFH. And then, the key genes were verified in another dataset, and the diagnostic value of key genes was evaluated by receiver operating characteristic (ROC) curve.
RESULTS
Nine gene co-expression modules were constructed via WGCNA. The brown module with 1258 genes was most significantly correlated with SONFH and was identified as the key module for SONFH. The results of functional enrichment analysis showed that the genes in the key module were mainly enriched in the inflammatory response, apoptotic process and osteoclast differentiation. A total of 91 genes were identified as hub genes in the key module. Besides, 145 DEGs were identified by DEGs screening and 26 genes were identified as hub genes of DEGs. Overlapping genes of hub genes in the key module and hub genes in DEGs, including RHAG, RNF14, HEMGN, and SLC2A1, were further selected as key genes for SONFH. The diagnostic value of these key genes for SONFH was confirmed by ROC curve. The validation results of these key genes in GSE26316 dataset showed that only HEMGN and SLC2A1 were downregulated in the SONFH group, suggesting that they were more likely to be diagnostic biomarkers of SOFNH than RHAG and RNF14.
CONCLUSIONS
Our study identified that two key genes, HEMGN and SLC2A1, might be potential diagnostic biomarkers of SONFH.
背景
类固醇诱导的股骨头坏死（SONFH）是一种慢性致残性骨病。本研究旨在揭示SONFH的新型诊断生物标志物。
方法
基于10名健康个体和30名SONFH患者外周血样本的GSE123568数据集用于加权基因共表达网络分析（WGCNA）和差异表达基因（DEG）筛选。提取与SONFH相关模块中的基因和DEG进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。选择基因显著性|>0.7且模块成员关系|>0.8的基因作为模块中的枢纽基因。选择连接度≥5的DEG作为DEG中的枢纽基因。随后，选择模块中的枢纽基因与DEG中的枢纽基因的重叠基因作为SONFH的关键基因。然后，在另一个数据集中验证关键基因，并通过受试者工作特征（ROC）曲线评估关键基因的诊断价值。
结果
通过WGCNA构建了9个基因共表达模块。包含1258个基因的棕色模块与SONFH的相关性最为显著，被确定为SONFH的关键模块。功能富集分析结果表明，关键模块中的基因主要富集于炎症反应、凋亡过程和破骨细胞分化。共有91个基因被确定为关键模块中的枢纽基因。此外，通过DEG筛选鉴定出145个DEG，26个基因被确定为DEG的枢纽基因。关键模块中的枢纽基因与DEG中的枢纽基因的重叠基因，包括RHAG、RNF14、HEMGN和SLC2A1，被进一步选为SONFH的关键基因。ROC曲线证实了这些关键基因对SONFH的诊断价值。这些关键基因在GSE26316数据集中的验证结果表明，SONFH组中只有HEMGN和SLC2A1下调，这表明它们比RHAG和RNF14更有可能是SOFNH的诊断生物标志物。
结论
我们的研究确定，两个关键基因HEMGN和SLC2A1可能是SONFH的潜在诊断生物标志物。
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