摘要
To identify novel genes in castration-resistant prostate cancer(CRPC),we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus(GEO).R packages affy and limma were performed to identify differentially expressed genes(DEGs)between primary prostate cancer and CRPC.After that,we performed functional enrichment analysis including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway.In addition,protein–protein interaction(PPI)analysis was used to search for hub genes.Finally,to validate the significance of these genes,we performed survival analysis.As a result,we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets.Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosteroneregulated sodium reabsorption pathway.PPI network identified hub genes like cortactin-binding protein 2(CTTNBP2),Rho family guanosine triphosphatase(GTPase)3(RND3),protein tyrosine phosphatase receptor-type R(PTPRR),Jagged1(JAG1),and lumican(LUM).Based on PPI network analysis and functional enrichment analysis,we identified two genes(PTPRR and JAG1)as key genes.Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer.In conclusion,PTPRR and JAG1 are key genes in the CRPC,which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
目的:鉴定去势抵抗性前列腺癌(CRPC)的关键基因。创新点:(1)结合多个数据库数据,运用生物信息学方法鉴定CRPC的关键基因;(2)首次报道PTPRR可能在CRPC里起关键作用。方法:通过下载三个GEO数据库的m RNA微阵列数据,分析CRPC和激素敏感前列腺癌之间的基因差异,对筛选出的差异基因进行功能富集分析和蛋白质间相互作用分析,最终筛选出两个有重要功能的差异基因(PTPRR和JAG1)。通过在多个其他数据库中进行表达量验证和生存分析,进一步证明这些基因的重要作用。结论:PTPRR和JAG1在CRPC中显著增高,并与预后差相关。因此,这两个基因有可能作为CRPC的诊断和预后的生物标志物。
