基于生物信息学方法对慢性鼻窦炎伴鼻息肉差异基因表达的分析

Differential gene expression in chronic rhinosinusitis with nasal polyps based on bioinformatics

  • 摘要:
      背景  慢性鼻窦炎伴鼻息肉是常见的慢性炎症性疾病,其术后复发率高,发病机制尚未完全明了。
      目的  通过生物信息学方法筛选出慢性鼻窦炎伴鼻息肉患者的息肉组织与正常对照鼻黏膜的差异基因,为慢性鼻窦炎伴鼻息肉的分子生物研究和生物标志物筛选提供理论依据。
      方法  从GEO数据集中选取GSE136825,提取出42例慢性鼻窦炎伴鼻息肉患者的息肉组织和28例健康对照者的鼻黏膜组织的高通量测序数据,利用R语言及Deseq2包分析差异表达基因,利用Metacore数据库进行差异基因的基因本体论(gene ontology,GO)富集分析和通路富集分析,并通过Cytoscape软件构建蛋白-蛋白相互作用网络,寻找在疾病中发挥作用的关键基因。
      结果  共筛选得到777个差异表达基因,其中上调基因527个,下调基因250个。对差异基因进行功能和通路富集分析,显示炎症反应、免疫受体活性、粒细胞趋化、金属肽酶活性等生物学功能在鼻息肉组织与正常黏膜组织之间存在显著相关性。进一步得到与CRSwNP相关的核心基因SCG2、IGFBP3、CA4、C3、SPP1、CP、CHRDL1、BPIFB2。以上核心基因中SCG2、IGFBP3、CA4、C3、SPP1、CP在鼻息肉组织中表达上调,CHRDL1、BPIFB2在鼻息肉组织中表达下调。
      结论  本研究有助于加强对慢性鼻窦炎伴鼻息肉相关分子机制的了解,为该疾病的临床和机制研究提供一定基础。

     

    Abstract:
      Background  Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease with complicated pathogenesis and high postoperative recurrence rate, and the pathogenesis has not yet been fully understood. Objective To analyze the differentially expressed genes (DEGs) and their biological function in the nasal polyps from patients with CRSwNP based on bioinformatics.
      Methods  In this study, we selected the GSE136825 in the GEO database and used the RNA-seq data from the 42 nasal polyps of CRSwNP patients and 28 nasal mucosa from healthy control subjects. R software and Deseq2 package were used to analyze the DEGs. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis were performed on the DEGs using the Metacore database. Protein-protein interaction networks (PPI) and the hub genes were constructed by Cytoscape software.
      Results  A total of 777 DEGs were screened from the transcriptomic data of nasal polyps and normal mucosal tissues (527 genes up-regulated and 250 genes down-regulated). GO and KEGG pathway enrichment analysis of differential genes showed that inflammatory response, immunoreceptor activity, granulocyte chemotaxis, metallopeptidase activity and other biological functions were significantly correlated between nasal polyp tissues and normal mucosal tissues. Furthermore, the core genes related to CRSwNP were SCG2, IGFBP3, CA4, C3, SPP1, CP, CHRDL1, and BPIFB2. Among the above core genes, SCG2, IGFBP3, CA4, C3, SPP1 and CP were up-regulated in nasal polyp tissues, while CHRDL1 and BPIFB2 were down-regulated.
      Conclusion  This study is helpful to enhance the understanding of the molecular mechanism of CRSwNP and provide a crucial basis for its clinical and mechanism research.

     

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