摘要
目的 应用生物信息学方法分析睾丸癌与正常组织之间的铁死亡相关差异基因和枢纽基因,为睾丸癌的预后和治疗提供新的思路和生物标记物。方法 从TCGA和GTEx数据库下载睾丸癌组织(n=148)和正常组织(n=165)的转录组数据。采用R语言对样本进行主成分分析(PCA),获取睾丸癌基因表达矩阵并筛选差异表达基因,并与铁死亡数据库(FerrDb)中483个铁死亡背景基因取交集基因,获取睾丸癌铁死亡差异表达基因并进行基因本体(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析;采用STRING数据库和Cytoscape软件构建蛋白质相互作用(PPI)网络,筛选前10个差异基因的关键枢纽基因并绘制基因热图;用GEPIA数据库分析枢纽基因在睾丸癌和正常组织的表达水平。从GEO数据库下载基因芯片GSE8607的转录组数据,用limma包进行差异分析,并提取前10个差异基因的表达谱数据,绘制睾丸癌相关的铁死亡差异基因热图进行验证。结果 差异表达分析共获得69个睾丸癌铁死亡相关差异基因,信号通路主要富集在铁死亡信号通路、NOD样受体信号通路、胞质DNA传感途径、JAKSTAT信号通路和Toll样受体信号通路;GO富集显示铁死亡相关的睾丸癌主要与氧化应激和对化学物质的应激反应相关。前10位铁死亡相关的睾丸癌枢纽基因在睾丸癌中表达量结果显示,TP53、IL-6、CD44、KRAS、HMOX1、PRDX1、SOX2和TXN在睾丸癌组织中升高,AR和GPX4表达量降低。GSE8607中提取的前10个关键基因的表达数据与TCGA联合GTEx数据分析结果一致。结论 睾丸癌铁死亡相关基因主要参与NOD样受体信号通路和JAK-STAT信号通路,TP53、IL-6、AR和GPX4可能是睾丸癌铁死亡相关治疗和预后的潜在生物标记物。
Objective To analyze ferroptosis-related differential genes and key genes between testicular germ cell tumors(TGCT)and normal tissues by using bioinformatics methods,and to provide new ideas and biomarkers for the prognosis and treatment of TGCT.Methods The transcriptome data of testicular cancer(n=148)and normal tissues samples(n=165)were downloaded from the TCGA and GTEx databases.R language was used for principal component analysis(PCA)to obtain the testicular cancer gene expression matrix and screen the differentially expressed genes,which intersect with 483 ferroptosis background genes in FerrDb to obtain the ferroptosis-related differentially expressed genes of testicular cancer,the KEGG pathway and GO enrichment analysis was used on ferroptosis-related differentially expressed genes.Then a protein interaction network(PPI)with the STRING database was constructed.Cytoscape software was used to screen the top 10 key hub genes of differential genes and the heat map of the top 10 genes were drawn with the pheatmap package.The expression levels of hub genes in testicular cancer and normal samples were analyzed using the GEPIA database.The transcriptome data of the gene chip GSE8607 was downloaded from the GEO database,the differential analysis was performed with the limma package,the expression profile data of the top 10 differential genes screened were extracted,and the heat map of the testicular cancer-related ferroptosis differential genes was drawn using the pheatmap package.Results 69 TGCT ferroptosis-related differential genes were obtained by differential expression analysis,and the signaling pathways were mainly enriched in the ferroptosis signaling pathway,the NOD-like receptor signaling pathway,the cytoplasmic DNA sensing pathway,the JAK-STAT signaling pathway,and the Toll-like receptor signaling pathway.GO enrichment showed that it was inseparable from oxidative stress and stress response to chemical substances.The top 10 hub genes in testicular cancer expression results showed TP53,IL-6,CD44,KRAS,HMO
作者
郭晓英
李玲
马慧颖
闫凤梅
郝羽
黄静
宋宜岚
GUO Xiaoying;LI Ling;MA Huiying;YAN Fengmei;HAO Yu;HUANG Jing;SONG Yilan(Department of Occupational and Environmental Health,School of Public Health and Management,Ningxia Medical University,Yinchuan 750004,China;Key Laboratory of Environmental Factors and Chronic Disease Control,School of Public Health and Management,Ningxia Medical University,Yinchuan 750004,China)
出处
《宁夏医科大学学报》
2023年第5期462-468,共7页
Journal of Ningxia Medical University
基金
宁夏自然科学基金项目(2021AAC03163)。
