Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head.
Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head.
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类固醇性股骨头坏死基因及分子通路的生物信息学分析及鉴定
DOI：
10.1186/s13018-021-02464-9
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发表时间：
2021-05-20
影响因子：
2.6
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Lin T;Chen W;Yang P;Li Z;Wei Q;Liang D;Wang H;He W;Zhang Q
激素性股骨头坏死是一种常见的髋关节疾病，早期诊断困难。目前激素性股骨头坏死的发病机制尚不清楚，缺乏公认有效的诊断标志物。本研究旨在寻找激素诱导的ONFH相关基因和信号通路，并探讨其分子机制。微阵列数据集GSE 123568（外周血）和GSE 74089（软骨）从Gene Expression Omnibus数据库获得，包括34个ONFH样品和14个对照样品。分别用Morpheus软件和Venn图鉴定DEG和共表达DEG。此外，我们进行了京都基因组百科全书（KEGG）和基因本体（GO）途径富集分析。我们通过GEO 2 R构建了一个蛋白质-蛋白质相互作用（PPI）网络，并使用cytoHubba将PPI网络划分为多个子网络。此外，进行定量实时聚合酶链反应（qRT-PCR）以验证生物信息学分析结果。在外周血和软骨样品之间共获得118个交叉DEG，包括40个上调基因和78个下调基因。然后，GO和KEGG途径富集分析显示，上调的DEG集中在与金黄色葡萄球菌感染、利什曼病、抗原加工和呈递以及哮喘和移植物抗宿主病相关的信号通路上。下调的基因集中在FoxO信号通路、AMPK信号通路、调节干细胞多能性的信号通路和mTOR信号通路。在PPI网络中发现了一些具有高度相互作用的枢纽基因，如CXCR 1、FPR 1、MAPK 1、FOXO 3、FPR 2、CXCR 2和TYROBP。qRT-PCR结果显示激素诱导的ONFH患者外周血中CXCR 1、FPR 1和TYROBP上调，而MAPK 1下调。这与生物信息学分析一致。本研究将为激素诱导的ONFH的基因和相关通路提供新的见解。CXCR 1、FPR 1、TYROBP和MAPK 1可作为激素诱导的ONFH诊断和预后的潜在药物靶点和生物标志物。
Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms. Microarray data sets GSE123568 (peripheral blood) and GSE74089 (cartilage) were obtained from the Gene Expression Omnibus database, including 34 ONFH samples and 14 control samples. Morpheus software and Venn diagram were used to identify DEGs and co-expressed DEGs, respectively. Besides, we conducted Kyoto Encyclopedia of Genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We construct a protein-protein interaction (PPI) network through GEO2R and used cytoHubba to divide the PPI network into multiple sub-networks. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the bioinformatics analysis results. A total of 118 intersecting DEGs were obtained between the peripheral blood and cartilage samples, including 40 upregulated genes and 78 downregulated genes. Then, GO and KEGG pathway enrichment analysis revealed that upregulated DEGs focused on the signaling pathways related to staphylococcus aureus infection, leishmaniasis, antigen processing, and presentation, as well as asthma and graft-versus-host disease. Downregulated genes were concentrated in the FoxO signaling pathway, AMPK signaling pathway, signaling pathway regulating stem cell pluripotency, and mTOR signaling pathway. Some hub genes with high interactions such as CXCR1, FPR1, MAPK1, FOXO3, FPR2, CXCR2, and TYROBP were identified in the PPI network. The results of qRT-PCR demonstrated that CXCR1, FPR1, and TYROBP were upregulated while MAPK1 was downregulated in peripheral blood of steroid-induced ONFH patients. This was consistent with the bioinformatics analysis. The present study would provide novel insight into the genes and associated pathways involved in steroid-induced ONFH. CXCR1, FPR1, TYROBP, and MAPK1 may be used as potential drug targets and biomarkers for the diagnosis and prognosis of steroid-induced ONFH.
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影响因子：
3
作者：
Kang S;Song J
通讯作者：
Song J
影响因子：
3.3
作者：
Park, Min Sung;Kim, Yun Hee;Lee, Jin Woo
通讯作者：
Lee, Jin Woo
影响因子：
5.3
作者：
Matsushita, Takehiko;Chan, Yuk Yu;Murakami, Shunichi
通讯作者：
Murakami, Shunichi
MMP9 中的单核苷酸多态性与类固醇诱导的股骨头坏死风险降低相关。
影响因子：
--
作者：
Du J;Liu W;Jin T;Zhao Z;Bai R;Xue H;Chen J;Sun M;Zhang X;Wang G;Wang J
通讯作者：
Wang J
影响因子：
23.9
作者：
Koelling, Sebastian;Kruegel, Jenny;Miosgel, Nicolai
通讯作者：
Miosgel, Nicolai