基于生物信息学方法筛选颈动脉粥样硬化进展的Hub基因及相关通路的研究

Screening of Hub genes and related pathways in the progression of carotid atherosclerosis based on bioinformatics

目的 利用生物信息学方法分析筛选颈动脉粥样硬化进展的Hub基因及相关通路。方法 通过基因表达公共数据库(GEO)下载GSE43292和GSE28829这2个数据集。应用R语言软件合并两者的基因表达数据并进行标准化处理后,筛选出早期与晚期颈动脉粥样硬化斑块组织的差异基因。对差异基因进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)信号通路富集分析。然后,利用STRING在线工具和Cytoscape软件构建并可视化差异基因的蛋白质-蛋白质相互作用(PPI)网络,再通过CytoHubba中3种常用的分析方法和Venn图法识别它们的共同Hub基因。结果 共筛选出576个差异基因,其中下调基因197个,上调基因379个。这些差异基因主要参与了中性粒细胞活化、中性粒细胞脱颗粒等GO生物过程。主要调控脂质和动脉粥样硬化、细胞因子-细胞因子受体相互作用等信号通路。最终在PPI网络中,共识别出3个Hub基因,分别是LYN、SYK和HCK。结论 LYN、SYK、HCK为颈动脉粥样硬化进展的关键基因,或可为该病的预后和治疗提供新的分子靶点。

Objective To analyze and screen the Hub gene and its related pathway in the progression of carotid atherosclerosis by bioinformatics.Methods Two datasets of GSE43292 and GSE28829 were downloaded from Gene expression Comprehensive Database.The differential genes of early and late carotid atherosclerotic plaques were screened by R language software combined with their gene expression data and standardized processing.The differential genes were annotated by gene ontology(GO) and enriched by Kyoto Encyclopedia of Gene and Genome(KEGG).Then, the protein-protein interaction(PPI) network of differential genes was constructed and visualized by STRING online tools and Cytoscape software, and Hub genes were screened out through overlapping the genes acquired from different algorithms of CytoHubba.Results A total of 576 differential genes were screened, including 197 down-regulated genes and 379 up-regulated genes.These differential genes are mainly involved in GO biological processes such as neutrophil activation and neutrophil degranulation.It mainly regulates lipid and atherosclerosis, cytokine-cytokine receptor interaction and other signal pathways.Finally, three Hub genes, LYN,SYK and HCK were identified in the PPI network.Conclusion LYN,SYK and HCK are the key genes in the progression of carotid atherosclerosis which may provide new molecular targets for the prognosis and treatment of the disease.