CDK1基因在肺动脉高压中表达和临床意义的生物信息学分析

Bioinformatics analysis of CDK1 gene expression and clinical significance in pulmonary hypertension

目的:通过生物信息学的方法分析筛选肺动脉高压(PAH)的关键基因。方法:通过GEO数据库下载GSE113439和GSE144274。依次进行GO、KEGG及GSEA进行功能及通路富集分析。利用String及Cytoscape软件建立蛋白互作(PPI)网络,进一步通过MCODE、CentiScape和CytoHubba插件筛选核心基因。结果:GSE113439中有544个DEGs(上调462个,下调82个),主要参与DNA双链解螺旋、DNA修复、有丝分裂核分裂等生物学过程。GSE144274中有1121个DEGs(上调702个,下调509个),主要参与细胞分裂、有丝分裂姐妹染色单体分离、染色体分离等生物学过程。两组数据集的DEGs均显著富集在细胞周期信号通路。建立PPI网络后,根据MCODE和CentiScape插件筛选出关键作用模块,根据MCC算法选择关键候选基因,并最终筛选出CDK1为关键基因。结论:CDK1是PAH的关键基因,可能成为PAH潜在的治疗靶点。

Objective: The present research aims to explore the hub gene of pulmonary arterial hypertension(PAH) through bioinformatic analysis. Methods: GSE113439 and GSE144274 were downloaded from GEO(gene expression omnibus) database. "Limma"in R package was used for selecting different expressed genes(DEGs). Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway and Gene Set Enrichment Analysis(GSEA) were sequentially performed to pick out the functional and differentially expressed pathways enrichment analysis. Protein-protein interaction(PPI) network was constructed through online tool String and Cytoscape software. The plug-in including MCODE, CentiScape and CytoHubba were utilized for selection of hub genes of PAH. Results: The 544 different expressed genes(DEGs) in GSE113439(462 upregulated and 82 downregulated) were selected out and they were enriched in DNA duplex unwinding, DNA repair and mitotic nuclear division in biological process(BP). The 1211 DEGs(702 upregulated and 509 downregulated) were selected out in GSE144274, and the DEGs were enriched in cell division, mitotic sister chromatid segregation and chromosome segregation in terms of BP. Consistently, DEGs were both significantly differentially enriched in cell cycle pathway in both GSE113439 and GSE144274. PPI network of the 544 DEGs of GSE113439 were constructed and then module 1 were picked out according to Molecular Complex Detection(MCODE) and CentiScape plug-in of Cytoscape. Maximal Clique Centrality(MCC) method in CytoHubba plug-in were utilized for selection of candidate genes. PPI network was also established in GSE144724, then followed by MCC method to select out the top 15 candidate genes, eventually CDK1 was ultimately selected as Hub gene. Conclusion: CDK1 is a key gene of PAH and it might exert as a potential therapeutic target for PAH.