慢性鼻窦炎鼻息肉基底干细胞转录组生物信息学分析

doi:10.6040/j.issn.1673-3770.0.2022.246

摘要/Abstract

摘要： 目的通过生物信息学技术对慢性鼻窦炎鼻息肉基底干细胞增殖分化过程中的差异表达基因分析,为慢性鼻窦炎鼻息肉上皮屏障损伤机制及治疗提供新的思路和方向。方法从基因表达数据库(GEO数据库)下载慢性鼻窦炎鼻息肉基底干细胞增殖分化转录组芯片数据集,使用R软件构建加权基因共表达网络分析(WGCNA)网络,筛选与正常对照组间与疾病相关的差异表达基因,通过网络在线工具DAVID进行差异基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,通过STRING数据库构建差异表达基因的蛋白相互作用网络,并应用Cytoscape中的MCODE插件对蛋白相互作用网络进行分析。最后,使用NetworkAnalys整合转录因子数据库构建核心基因的转录因子网络。结果研究发现基底干细胞在慢性鼻窦炎伴鼻息肉组与正常对照组间共有175个与疾病相关的差异表达基因(P<0.05,∣logFC∣>1)。GO分析和KEGG通路分析显示,这些差异基因主要富集在内肽酶活性的负调控、丝氨酸型内肽酶抑制剂活性和Wnt信号通路等。通过蛋白相互作用网络的构建及分析,筛选出IVL和SPRR2A等核心基因,它们均在基底干细胞分化过程中上调,且之间存在相互作用。GSEA分析表明,β-丙氨酸代谢可能参与慢性鼻窦炎鼻息肉的致病机制。此外,分析显示转录因子GATA2在基底干细胞分化过程中发挥关键作用。结论〓IVL、SPRR2A及GATA2转录因子可能参与了慢性鼻窦炎鼻息肉上皮屏障的损伤机制,内肽酶活性抑制可能是上皮屏障损伤的关键因素,此研究为进一步深入理解慢性鼻窦炎鼻息肉上皮屏障损伤的生物学机制及治疗提供了新思路。

关键词: 慢性鼻窦炎, 上皮屏障, 基底干细胞, 生物信息学

Abstract: Objective The differentially expressed genes(DEGs)involved in the proliferation and differentiation of basal stem cells(BSCs)of individuals with chronic rhinosinusitis with nasal polyps(CRSwNP)were analyzed using bioinformatics to identify the mechanisms underlying the epithelial barrier damage in CRSwNP and to gain insights for potential treatment strategies. Methods The transcriptome chip microarray dataset of the proliferation and differentiation of BSCs of nasal polyps was downloaded from the gene expression omnibus(GEO)database. R software was then used for weighted gene co-expression network analysis(WGCNA)to build networks and screen disease-associated genes on the basis of their differential expression between the CRSwNP group and the normal control group, and the online tool DAVID was used to perform gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment of the DEGs. A protein interaction network of the DEGs was constructed using the STRING database and analyzed by applying the MCODE plugin in Cytoscape software. Finally, a transcription factor network of core genes was constructed using the NetworkAnalyst tool and by integrating the transcription factor database. Results This study found that a total of 175 disease-associated genes showing differential expression between the BSC of the CRSwNP and normal control groups(P<0.05, ∣logFC∣>1). GO and KEGG pathway analysis revealed that these DEGs were mainly enriched in the negative regulation of endopeptidase activity, serine-type endopeptidase inhibitor activity, and the Wnt signaling pathway. Analysis of the constructed protein interaction network was performed to identify core genes such as IVL and SPRR2A. These genes were all upregulated during the differentiation of BSCs, and they were found to interact with each other. Furthermore, this analysis revealed that the transcription factor GATA2 plays a critical role in the differentiation of BSCs. Conclusion IVL, SPRR2A, and GATA2 may be involved in the mechanism through which the epithelial barrier is damaged in CRSwNP. Inhibition of endopeptidase activity may be the key mechanism involved in the epithelial barrier damage. This study provides new insights into the biological mechanism underlying the epithelial barrier damage in CRSwNP and our findings could help develop a treatment strategy for CRSwNP.

Key words: Chronic sinusitis, Epithelial barrier, Basal stem cells, Bioinformatics

中图分类号:

R765.4+1

王明明,罗洋,贺少娟,张现兴,李学忠. 慢性鼻窦炎鼻息肉基底干细胞转录组生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 6-15.

WANG Mingming, LUO Yang, HE Shaojuan, ZHANG Xianxing, LI Xuezhong. Bioinformatic analysis of the transcriptome of basal stem cells of individuals with chronic rhinosinusitis with nasal polyps[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(5): 6-15.

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