基于生物信息学整合分析探讨青光眼高压反应性视神经星形胶质细胞相关核心基因

Hub Genes of Astrocyte Involved in Glaucoma with Ocular Hypertension by Integrated Bioinformatics Analysis

  • 摘要:
    目的本研究旨在挖掘星形胶质细胞对于青光眼伴高眼压影响的潜在关键候选基因和相关通路。
    方法整合并深入分析表达谱GSE2378和GSE758,其中包括26例正常对照的27例高压反应性视神经星形胶质细胞(ONHA)。对差异表达的基因(DEG)进行分选,分析候选基因和富集途径,并进行DEGs相关的蛋白质相互作用(PPI)网络分析。
    结果从281个常见变化的DEG中共鉴定出119个一致表达的基因,其中包括68个表达上调基因和51个表达下调基因。119个表达一致的基因中,有75个(43个表达上调基因和32个表达下调基因)构成PPI网络,形成了117个蛋白相互作用的关系,并鉴定了10个核心基因。经PPI网络互作分析鉴定了3个相关性模块,通路富集分析显示模块1与细胞外的外泌体相关,模块2主要与抗体依赖性细胞毒性(ADCC)相关,模块3主要与Hippo信号传导途径相关。
    结论采用整合生物信息学分析,确定了星形胶质细胞参与青光眼合并高眼压的DEGs相关候选基因和相关通路,这可以提高我们对病因和潜在分子事件的认识,这些候选基因和通路可能是青光眼的治疗靶点。

     

    Abstract:
    ObjectiveThis study was conducted to elucidate the potential key candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension.
    MethodsExpression profiles GSE2378 and GSE758 including 27 reactive optic nerve head astrocytes (ONHAs) by hypertensions and 26 normal controls, were integrated and deeply analyzed. Differentially expressed genes (DEGs) were sorted and candidate genes and pathways enrichment were analyzed. DEGs-associated protein-protein interaction network (PPI) was performed.
    ResultsA total of 119 consistently expressed genes were identified from 281 commonly changed DEGs, including 68 up-regulated genes and 51 down-regulated genes. PPI network complex filtered 75 DEGs (43 up-regulated and 32 down-regulated genes) of the 119 consistently altered DEGs and developed 117 edges, and 10 hub genes were identified. The most significant 3 modules were filtered from PPI, pathway enrichment analysis showed that module 1 was associated with extracellular exosome. Module 2 was mainly associated with antibody-dependent cellular cytotoxicity (ADCC) and module 3 was mainly associated with Hippo signaling pathway.
    ConclusionTaken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension, which could improve our understanding of the cause and underlying molecular events, and these candidate genes and pathways could be therapeutic targets for glaucoma.

     

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