基于生物信息学分析骨肉瘤肺转移的关键基因和功能鉴定  

Identification of key genes and functions in lung metastasis of osteosarcoma based on bioinformatics

作　　者：王鑫[1] 彭李华[1] 陈兴旺 WANG Xin;PENG Li-hua;CHEN Xing-wang(Department of Orthopaedics,Bishan Hospital of Chongqing Medical University,Chongqing 402760,China)

机构地区：[1]重庆医科大学附属璧山医院骨科,重庆402760

出　　处：《中国骨伤》2024年第7期718-724,共7页China Journal of Orthopaedics and Traumatology

摘　　要：目的:采用生物信息学的方法筛选骨肉瘤肺转移的差异表达基因,并探讨其功能及调控网络。方法:从GEO数据库(http://www.ncbi.nlm.nih.gov/gds)中筛选数据集GSE14359,使用GEO2R在线工具筛选差异表达基因(differentially expressed gene,DEG);在线HMMD数据库(http://www.cuilab.cn/hmdd)下载骨肉瘤疾病相关的miRNA,FunRich软件预测靶基因,与DEG取交集,获得目标基因;根据靶向关系形成miRNA-mRNA关系对,数据导入Cytoscape可视化;DAVID对目标基因行GO和KEGG通路富集分析;STRING构建PPI网络,Cytoscape可视化,CytoHubba插件筛选中枢基因,在线网站进行表达和生存分析。结果:共鉴定出704个DEG,由477个上调基因和227个下调基因组成。FunRich预测出mRNA 7888个,两者交集,获得目标基因343个。KEGG富集分析显示:目标基因主要参与焦点粘连、细胞外基质(extracellularmatrix,ECM)受体相互作用、肿瘤坏死因子(trmor necrosis factor,TNF)信号通路、PI3K-Akt信号通路、白细胞介素-17(interleukin 17,IL-17)信号通路、MAPK信号通路。获得10个中枢基因(CCNB1、CHEK1、AURKA、DTL、RRM2、MELK、CEP55、FEN1、KPNA2、TYMS),CCNB1、DTL、MELK和预后不良高度相关。结论:该研究确定的关键基因和功能通路可能有助于了解骨肉瘤肺转移癌发生和进展的分子机制,并提供潜在的治疗靶点。Objective To screen the differentially expressed genes of lung metastasis of osteosarcoma by bioinformatics,and explore their functions and regulatory networks.Methods The data set of GSE14359 was screened from GEO database(http://www.ncbi.nlm.nih.gov/gds)and the differentially expressed gene(DEG)was identified using GEO2R online tool.Download osteosarcoma disease related miRNAs from the online HMMD database(http://www.cuilab.cn/hmdd)and then FunRich software was used to predict the target gene,intersects with DEG to obtains the target gene.The miRNA-mRNA relationship pairs were formed according to the targeted joints,then the data was imported into Cytoscape for visualization,DAVID was used to performe GO and KEGG analysis on target genes,STRING was used to construct PPI network,Cytoscape visualization,CytoHubba plug-in screening central genes and online website for expression and survival analysis.Results Total 704 DEGs were identified,consisting of 477 up-regulated genes and 227 down regulated genes.FunRich predicted 7888 mRNAs and 343 target genes were obtained through intersection of the two.KEGG analysis showed that it was mainly involved in focal adhesion,ECM receptor interaction,TNF signal pathway,PI3K-Akt signal pathway,IL-17 signal pathway and MAPK signal pathway.Ten central genes(CCNB1,CHEK1,AURKA,DTL,RRM2,MELK,CEP55,FEN1,KPNA2,TYMS)were identified as potential key genes.Among them,CCNB1,DTL,MELK were highly correlated with poor prognosis.Conclusion The key genes and functional pathways identified in this study may be helpful to understand the molecular mechanism of the occurrence and progression of lung metastases from osteosarcoma,and provide potential therapeutic targets.

关 键 词：骨肉瘤 肺转移 生物信息学 基因 

分 类 号：R681[医药卫生—骨科学]