Department of Pathology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
J Zhejiang Univ Sci B. 2020;21(3):246-255. doi: 10.1631/jzus.B1900329.
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 aldosterone-regulated 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.
为了鉴定去势抵抗性前列腺癌(CRPC)中的新基因,我们从基因表达综合数据库(GEO)下载了包含 CRPC 和原发性前列腺癌的三个微阵列数据集。使用 R 包 affy 和 limma 来鉴定原发性前列腺癌和 CRPC 之间的差异表达基因(DEGs)。之后,我们进行了功能富集分析,包括基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路。此外,还进行了蛋白质-蛋白质相互作用(PPI)分析,以搜索枢纽基因。最后,为了验证这些基因的重要性,我们进行了生存分析。结果,我们鉴定了至少在两个数据集中发生变化的 53 个上调基因和 58 个下调基因。功能富集分析显示,成骨细胞分化途径的正调控和醛固酮调节的钠重吸收途径发生了显著变化。PPI 网络鉴定了枢纽基因,如皮层结合蛋白 2(CTTNBP2)、Rho 家族鸟苷三磷酸酶(GTPase)3(RND3)、蛋白酪氨酸磷酸酶受体型 R(PTPRR)、Jagged1(JAG1)和亮氨酸(LUM)。基于 PPI 网络分析和功能富集分析,我们鉴定了两个关键基因(PTPRR 和 JAG1)。进一步的生存分析表明,这两个基因的高表达与前列腺癌预后不良有关。总之,PTPRR 和 JAG1 是 CRPC 的关键基因,可能成为 CRPC 诊断和预后的有前途的生物标志物。