前列腺癌骨转移关键基因的生物信息学分析

Bioinformatics analysis of key genes in prostate cancer bone metastasis

目的:利用生物信息学技术探究前列腺癌骨转移发生发展的分子机制,为前列腺癌骨转移提供新的预防和治疗靶点。方法:从基因表达数据库(GEO)检索筛选得到包含20例前列腺癌骨转移样本和69例前列腺癌淋巴结转移样本的基因芯片数据集GSE74685。利用R语言Limma包对原始数据进行预处理并筛选差异表达基因(DEGs)。通过基因功能注释在线工具DAVID对DEGs进行GO功能富集分析和KEGG通路富集分析。利用STRING在线检索工具及Cytoscape软件构建DEGs的蛋白质-蛋白质相互作用(PPI)网络,并用MCODE和cytoHubba插件筛选重要模块和关键基因。通过HCMDB和GEPIA数据库验证关键基因的表达、生存预后以及诊断价值。结果:从GSE74685数据集中筛选出2022个DEGs,包括842个上调基因和1180个下调基因。GO功能富集分析显示DEGs主要在细胞外基质组织、胶原分解代谢过程、对机械刺激的反应、中性粒细胞趋化性的正调控方面富集;KEGG通路富集提示黏着斑、细胞外基质受体相互作用是DEGs富集的主要信号通路。通过PPI网络筛选得到11个关键基因,分别为EZH2、PLG、SRC、CAV1、CHD4、HIST2H2BE、KDM1A、POLR2E、VWF、APOE、THBS1。对11个关键基因的基因表达验证和生存分析发现APOE和EZH2与前列腺癌骨转移密切相关。结论:EZH2、APOE可能参与前列腺癌骨转移的发生发展,可以作为潜在的治疗靶点,为前列腺癌骨转移的预防和治疗提供新的研究方向。

Objective:To explore the molecular mechanism of prostate cancer bone metastasis by bioinformatics,and to provide a new target for prevention and treatment of prostate cancer bone metastasis.Methods:The dataset GSE74685 containing 20 cases of prostate cancer bone metastasis and 69 cases of prostate cancer lymph node metastasis were retrieved and screened from the Gene Expression Database(GEO).The Limma package of R software is used to preprocess the original data and screen differentially expressed genes(DEGs).DEGs were analyzed by GO function enrichment and KEGG pathway enrichment analysis through the gene function annotation online tool DAVID.The protein-protein interaction(PPI)network of DEGs was constructed by using the STRING online retrieval tool and Cytoscape software.And the important modules and key genes were screened by using MCODE and cytoHubba plug-ins.The expression,prognosis and diagnostic value of key genes were verified by HCMDB and GEPIA database.Results:A total of 2022 DEGs were selected from the dataset GSE74685,including 842 up-regulated genes and 1180 down-regulated genes.GO functional enrichment analysis showed that DEGs were mainly enriched in the extracellular matrix organization,collagen catabolic process,response to mechanical stimulus,and positive regulation of neutrophil chemotaxis.KEGG pathway enrichment suggested that focal adhesion and ECM-receptor interaction were the main signal pathway for DEGs enrichment.Eleven key genes,EZH2,PLG,SRC,CAV1,CHD4,HIST2H2BE,KDM1A,POLR2E,VWF,APOE and THBS1 were obtained through PPI network screening.The verification of gene expression and survival analysis of 11 key genes showed that APOE and EZH2 were closely related to prostate cancer bone metastasis.Conclusion:EZH2 and APOE may be involved in the occurrence and development of prostate cancer bone metastasis,which can be used as potential therapeutic targets and provide a new research direction for the prevention and treatment of prostate cancer bone metastasis.