基于生物信息学分析骨肉瘤转移的关键基因及预后

Analysis of Key Genes and Prognosis of Osteosarcoma Metastasis Based on Bioinformatics

目的:通过生物信息学分析筛选出骨肉瘤转移的关键基因,探讨骨肉瘤转移潜在的机制和关键标志物。方法:从TARGET数据库中下载骨肉瘤基因表达谱和临床信息数据,采用R软件的“limma”包筛选骨肉瘤转移组和非转移组的差异基因(Difference genes,DEGs),对差异基因运用R软件的“clusterProfiler”包进行基因本体论(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析,了解DEGs富集的分子功能及通路,采用STRING数据库构建蛋白-蛋白相互作用(Protein-Protein inter-action network,PPI)网络,采用Cytoscape软件对DEGs进行相关性分析,找出与骨肉瘤转移进展最相关的核心基因(Hub gene);对Hub基因进行Kaplan-Meier(K-M)生存分析,明确和验证Hub基因与骨肉瘤患者预后之间的关系,筛选出对预后具有意义的关键基因。结果:分析出248个有差异表达的基因,其中上调18个、下调230个差异基因,GO分析发现主要涉及肌肉组织、器官、系统的发育和横纹肌组织发育,KEGG信号通路主要参与肌动蛋白细胞骨架的调节、Ras信号通路、PI3K-Akt信号通路和MAPK信号通路,通过PPI网络分析筛选得到20个关键基因,生存分析显示PLCB4的高表达与骨肉瘤患者的不良预后显著相关。结论:PLCB4可能参与骨肉瘤转移,并与预后显著相关,可能成为骨肉瘤患者预后和治疗的潜在靶点。

Objective:To screen out the key genes of osteosarcoma metastasis by bioinformatics analysis and to explore the potential mechanism and key markers of osteosarcoma metastasis.Methods:Download osteosarcoma gene expression profile and clinical information data from TARGET database.We used the"limma"package of R software to screen the difference genes(DEGs)of osteosarcoma metastasis group and non-metastatic group which was analysed by the R language"clusterProfiler"for gene ontology(Gene Ontology,GO),Kyoto gene and genome encyclopedia(Kyoto Encyclopedia of Genes and Genomes,KEGG).So we can understand the molecular functions and pathways of DEGs enrichment.A protein-protein interaction(Protein-Protein inter-action network,PPI)network was constructed by the STRING database.To identify the core genes(Hubs)most associated with the progression of osteosarcoma metastasis,the correlation between DEGs enrichment was analyzed by Cytoscape software.Kaplan-Meier(K-M)survival analysis of Hub gene was carried out to clarify and verify the relationship between Hub gene and the prognosis of osteosarcoma patients,and to screen key genes that have significance for prognosis.Results:248 differentially expressed genes were analyzed,including 18 up-and 230 differentiated.The genes are mainly involved in the development of muscle tissue,organs,systems and rhabdomyomuscular tissue by GO analysis.The KEGG signaling pathway is mainly involved in the regulation of actin cytoskeleton,Ras signaling pathway,PI3K-Akt signaling pathway and MAPK signaling pathway.20 key genes screened by protein interaction network analysis were operated Survival analysis,which showed high expression of PLCB4 was significantly associated with poor prognosis in patients with osteosarcoma.Conclusion:PLCB4 may be involved in osteosarcoma metastasis and significantly correlated with prognosis,which may become a potential target for prognosis and treatment in patients with osteosarcoma.