机构地区:[1]萍乡卫生职业学院医学技术学院,江西省萍乡市337000
出 处:《医学理论与实践》2025年第6期906-912,共7页The Journal of Medical Theory and Practice
基 金:江西省教育厅科学技术研究项目(GJJ2210014)。
摘 要:目的:基于生物信息学分析研究c-MYC和lncRNA数据协同调控肝细胞癌(HCC)发生发展的分子机制和生存预后的关键基因。方法:从基因表达综合数据库(GEO)筛选下载与HCC相关的c-MYC和lncRNA基因表达数据集(GSE12443和GSE101728)。利用GEO2R分组处理和Venn图鉴定差异表达基因(DEGs)。通过注释、可视化和综合发现数据库(DAVID)对DEGs进行了基因本体论(GO)功能分析和京都基因组百科全书(KEGG)通路富集分析。在STRING数据库中构建蛋白—蛋白互作网络(PPI)图,使用Cytoscape8.0软件进行网络可视化,使用Cytoscape的插件MCODE得出核心模块,同时使用CytoHubba筛选关键基因。使用基因表达谱交互分析(GEPIA)和Kaplan-Meier Plotter在线数据库对TCGA HCC数据集的关键基因进行验证。此外,通过人类蛋白质图谱(HPA)数据库用于验证关键基因的蛋白质表达水平。结果:共筛选出41个DEGs,其中上调基因23个,下调基因18个。GO分析表明DEGs主要参与RNA聚合酶Ⅱ启动子、胞质溶胶和蛋白质结合转录的正调控。KEGG通路富集分析表明,DEGs主要富含代谢通路、PI3K-Akt信号通路、人瘤病毒感染以及癌症和沙门菌感染通路。在PPI网络图中,使用MCODE插件检测得分较高的子网络。鉴定出10个关键基因是CDK1、CDC20、KIF11、BUB1、KIF20A、CDCA8、AURKB、BIRC5、CENPA和ASPM。其他公共数据库证实,上述基因的高表达与HCC患者的总生存率低有关。结论:所鉴定的关键基因和通路与HCC的发病机制有关,可为未来HCC的分子靶向治疗和预后评估提供新的思路。此外,这些关键基因和通路还可能是HCC治疗的潜在靶点。Objective:The hub genes of c-MYC and lncRNA dataset that synergistically regulate the molecular mechanism of HCC development as well as the prognosis of survival were investigated by bioinformatics analysis.Methods:Data related to gene expression of c-MYC and lncRNA in HCC tissues or cells were screened and downloaded from the gene expression omnibus(GEO)database(GSE12443 and GSE101728).The differentially expressed genes(DEGs)were identified using GEO2R group processing and Venn diagrams,gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG).Pathway enrichment analysis of DEGs was performed using the database for annotation,visualization and integrated discovery(DAVID)database.After constructing the protein-protein interaction(PPI)network relationship map in the search tool for the retrieval of interacting genes(STRING)database,Cytoscape8.0 software was used for network visualization using the plug-in molecular complex detection(MCODE)in Cytoscape to derive the core modules while CytoHubba was used to screen the hub genes.The hub genes were verified using gene expression profiling interactive analysis(GEPIA)and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset.Moreover,the human protein atlas(HPA)database was used to verify candidate genes’protein expression levels.Results:A total of 41 common DEGs were screened,including 23 up-regulated genes and 18 down-regulated genes.Moreover,GO analysis implied that DEGs were mainly involved in the positive regulation of transcription from RNA polymeraseⅡpromoter,cytosol,and protein binding.KEGG pathway enrichment analysis presented that DEGs were mainly enriched in metabolic pathways,PI3K-Akt signaling pathway,human papillomavirus infection,and pathways in cancer and salmonella infection.In the PPI network,two subnetworks with high scores were detected using the MCODE plugin.The top 10 hub genes identified were CDK1,CDC20,KIF11,BUB1,KIF20A,CDCA8,AURKB,BIRC5,CENPA,and ASPM.The other public databases co
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