基于生物信息学分析的圆锥角膜相关Hub基因及其通路的鉴定

Identification of keratoconus-associated Hub genes and their pathways based on bioinformatics analysis

目的:明确圆锥角膜(KC)潜在的目标基因并探讨其潜在的病理机制。方法:从GEO数据库中下载GSE77938的基因芯片数据并进行生物信息学分析。GSE77938数据集包含50个样本,包括25例KC患者和25例正常对照者。采用Cytoscape软件进行GO和KEGG富集分析,并通过Cytoscape软件构建差异表达基因(DEGs)的蛋白相互作用(PPI)网络。结果:在KC中共鉴定出1547个DEGs,包括1103个上调基因和444个下调基因。GO分析结果显示,上调的DEGs在生物过程(BP)中的1220条通路中显著富集、细胞成分(CC)的黑素体的102条通路和分子功能(MF)的102条通路中显著富集。下调DEGs的富集功能在BP、CC和MF中分别为99、64和47个通路。KEGG通路分析显示上调的DEGs富集于72条通路,而下调的DEGs富集于8条通路。从PPI网络中鉴定出Hub基因TNF、JUN、IFNG、PTPRC、ICAM1、FOS、IL6、CXCL8、LCK、CSF2、MMP9、ITGAX、CD40LG和IL10,ClueGO分析发现这些基因涉及GO术语中的6条显著通路和KEGG中的3条通路。结论:所鉴定的DEGs和枢纽基因促进了对KC发生的分子机制的理解,其可能作为KC治疗的分子靶点和诊断性生物标志物。

Objective:To identify the keratoconus(KC)-associated potential target genes and to explore their potential mechanisms.Methods:The affymetrix microarray data of GSE77938 were downloaded from GEO database for further analysis.The GSE77938 dataset contained 50 samples,including 25 keratoconus patients and 25 normal controls.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analyses were performed,and protein-protein interaction(PPI)network of the differentially expressed genes(DEGs)was constructed by Cytoscape software.Results:In total,1547 DEGs were identified in keratoconus,including 1103 up-regulated genes and 444 downregulated genes.GO analysis results showed that upregulated DEGs were significantly enriched in 1220 pathways in biological processes(BP),102 pathways in melanosome in celelular component(CC)and 102 pathways in Molecular function(MF).The enriched functions of downregulated DEGs were 99 pathways in BP,64 in CC and 47 in MF respectively.KEGG pathway analysis showed the up-regulated DEGs were enriched in 72 pathways,while the down-regulated DEGs were enriched in 8 pathways.The Hub genes,TNF,JUN,IFNG,PTPRC,ICAM1,FOS,IL6,CXCL8,LCK,CSF2,MMP9,ITGAX,CD40LG and IL10 were identified from the PPI network,and ClueGO analysis revealed that these genes were involved 6 significant pathways in GO terms and 3 pathways in KEGG.Conclusion:The identified DEGs and hub genes have promoted our understanding of the molecular mechanisms underlying the development of keratoconus,and might be used as molecular targets and diagnostic biomarkers for the treatment of keratoconus.