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基于全基因组表达谱鉴定股骨头坏死髋关节软骨中的差异表达基因。

Identification of differentially expressed genes in hip cartilage with femoral head necrosis, based on genome‑wide expression profiles.

机构信息

Department of Pediatric Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.

Department of Orthopedics, Development Zones Center Hospital of Heze, Heze, Shandong 27400, P.R. China.

出版信息

Mol Med Rep. 2019 Sep;20(3):2073-2082. doi: 10.3892/mmr.2019.10458. Epub 2019 Jul 2.

Abstract

Necrosis of the femoral head (NFH), a severe orthopedic disease in adults, involves the collapse of the femoral head. The pathophysiological mechanisms underlying NFH are yet to be fully investigated. The aim of the present study was to identify potentially important genes and signaling pathways involved in NFH and investigate their molecular mechanisms. Gene expression profiles of patients with NFH and healthy controls were compared using the Gene Expression Omnibus (GEO) database repository of the National Center of Biotechnology Information. GSE74089 from the GEO database included 4 patients with NFH and 4 healthy individuals. A total of 1,191 differentially expressed genes (DEGs) were identified between the patients with NFH and controls, including 743 upregulated and 448 downregulated DEGs. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that upregulated DEGs were mainly involved in the phosphoinositide 3‑kinase/protein kinase B signaling pathway, focal adhesion and extracellular matrix‑receptor interactions. Additionally, protein‑protein interaction (PPI) analysis identified the most central DEGs as vascular endothelial growth factor A, Jun proto‑oncogene, cyclin D1, fibroblast growth factor 2, HECT domain and ankyrin repeat‑containing E3 ubiquitin protein ligase 1, protein kinase Cα, bone morphogenetic protein 2 and prostaglandin‑endoperoxide synthase 2. PPI analysis also identified guanine nucleotide‑binding protein, γ13 as the most commonly downregulated gene based on different centrality. The results of the present study may provide novel insight into the genes and associated pathways involved in NFH, and aid the identification of novel therapeutic targets and biomarkers in the treatment of NFH.

摘要

股骨头坏死(NFH)是一种严重的成人骨科疾病,涉及股骨头塌陷。NFH 的病理生理机制尚未得到充分研究。本研究旨在鉴定与 NFH 相关的潜在重要基因和信号通路,并研究其分子机制。使用美国国立生物技术信息中心的基因表达综合数据库(GEO)数据库存储库比较 NFH 患者和健康对照的基因表达谱。GEO 数据库中的 GSE74089 包含 4 名 NFH 患者和 4 名健康个体。在 NFH 患者和对照组之间共鉴定出 1191 个差异表达基因(DEG),包括 743 个上调 DEG 和 448 个下调 DEG。然后,GO 和京都基因与基因组百科全书通路富集分析显示,上调的 DEG 主要参与磷酸肌醇 3-激酶/蛋白激酶 B 信号通路、焦点黏附和细胞外基质-受体相互作用。此外,蛋白质-蛋白质相互作用(PPI)分析确定血管内皮生长因子 A、原癌基因 Jun、周期蛋白 D1、成纤维细胞生长因子 2、HECT 结构域和锚蛋白重复含 E3 泛素蛋白连接酶 1、蛋白激酶 Cα、骨形态发生蛋白 2 和前列腺素内过氧化物合酶 2 为最核心的 DEG。PPI 分析还根据不同的中心性确定了鸟嘌呤核苷酸结合蛋白 γ13 为最常见的下调基因。本研究的结果可能为 NFH 相关基因和相关通路提供新的见解,并有助于鉴定 NFH 治疗的新治疗靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5352/6691263/fab801195ec0/MMR-20-03-2073-g00.jpg

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