机构地区:[1]内蒙古科技大学包头医学院第一附属医院呼吸与危重症医学科,内蒙古包头014040 [2]内蒙古科技大学包头医学院,内蒙古包头0140100
出 处:《癌症进展》2024年第7期745-753,共9页Oncology Progress
基 金:包头市卫生健康科技计划项目(wsjkkj009);公立医院科研联合基金科技项目(2023GLLH0206)。
摘 要:目的基于基因表达综合(GEO)数据库和癌症基因组图谱(TCGA)数据库筛选肺腺癌(LUAD)预后相关基因。方法从GEO数据库中筛选出GSE118370、GSE10072、GSE1150023个数据集,使用R软件筛选LUAD组织和相邻正常肺组织中的差异基因,对差异基因进行基因本体(GO)及京都基因和基因组百科全书(KEGG)通路富集分析。应用STRING数据库构建与差异基因相关的蛋白质-蛋白质相互作用(PPI)网络。应用Cytoscape软件鉴定差异基因中的关键基因,采用基因表达谱交互式分析(GEPIA)数据库分析关键基因在LUAD组织和正常肺组织中的表达,比较关键基因高表达与低表达LUAD患者的总生存期和无病生存期,比较不同临床分期LUAD患者关键基因的表达情况。应用UALCAN数据库对LUAD组织和正常肺组织中关键基因的表达情况进行分析。结果共获得101个上调差异基因和213个下调差异基因。GO富集分析结果显示,上调差异基因主要富集在细胞外基质组织、有丝分裂细胞周期、上皮细胞分化等生物过程中,以及细胞黏附分子结合、蛋白激酶结合等分子功能方面;KEGG通路富集分析结果显示,上调差异基因主要富集在p53信号通路、松弛素信号通路等通路。GO富集分析结果显示,下调差异基因主要富集在血管发育、细胞对细胞因子刺激的反应等生物过程中,以及细胞外基质和膜筏等细胞组成中;KEGG通路富集分析结果显示,下调差异基因主要富集在细胞因子-细胞因子受体相互作用、神经活性配体-受体相互作用等通路中。最终筛选出8个关键基因,分别是BUB1有丝分裂检查点丝氨酸/苏氨酸激酶B(BUB1B)、ZW10相互作用着丝点蛋白(ZWINT)、细胞周期蛋白依赖性激酶1(CDK1)、DNA拓扑异构酶Ⅱα(TOP2A)、泛素结合酶E2C(UBE2C)、细胞周期蛋白B2(CCNB2)、NIMA相关激酶2(NEK2)、纺锤体微管的装配因子(ASPM)。这8个基因在LUAD组织中的表达水平均高于正常�Objective To screen prognostic-related genes of lung adenocarcinoma(LUAD)based on Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)databases.Method Three datasets GSE118370,GSE10072 and GSE115002 were selected from GEO database.R software was usd to screen differential genes in LUAD tissues and adjacent normal lung tissues,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for differential genes.STRING database was used to construct protein-protein interaction(PPI)networks associated with differential genes.The key genes in differential genes were identified by the software Cytoscape,and the expression of key genes in LUAD tissues and normal lung tissues were analyzed by Gene Expression Profiling Interactive(GEPIA)database.The overall survival and disease-free survival of LUAD patients with high and low expression of key genes were compared.The expression of key genes in LUAD patients with different clinical stages were compared.UALCAN database was used to analyze the expression of key genes in LUAD tissues and normal lung tissues.Result A total of 101 up-regulated differential genes and 213 down-regulated differential genes were obtained.GO enrichment analysis showed that up-regulated differential genes were mainly enriched in biological processes such as extracellular matrix tissues,mitotic cell cycle,epithelial cell differentiation,as well as molecular functions such as cell adhesion molecule binding and protein kinase binding.KEGG pathway enrichment analysis showed that upregulated differential genes were mainly enriched in pathway such as p53 signaling pathway and relaxin signaling pathway.GO enrichment analysis showed that down-regulated differential genes were mainly enriched in biological processes such as vascular development,cell response to cytokine stimulation,and cellular components such as extracellular matrix and membrane rafts.The KEGG pathway enrichment analysis showed that down-regulated differential genes were mainly enriched
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