Tan Jiufeng, Jin Xuefei, Wang Kaichen
Department of urology, China-Japan Union Hospital of Jilin University, 126 Xiantai ST, Changchun, Jilin Province, 130033, China.
Pathol Oncol Res. 2019 Apr;25(2):455-460. doi: 10.1007/s12253-017-0346-8. Epub 2017 Dec 19.
The aim was to expound the pathogenesis of prostate cancer and to identify the potentially biomarkers for prostate cancer (PC). DNA methylation microarray data GSE38240 containing 8 prostate cancer metastases and 4 normal prostate samples as well as gene expression profile data GSE26910 containing 6 prostate primary tumors and 6 normal samples were used. Differentially expressed genes (DEGs) and differently methylated sites of PC were screened and the regulatory network was constructed with DEGs-related transcription factors (TFs). The obtained hub genes were subjected to protein-protein interaction network analysis. Enrichment analysis of down-regulated DEGs were performed. Total 351 DEGs including 190 down-regulated and 161 up-regulated genes and 3234 differently methylated sites were identified. In total 69 DEGs-related TFs were found. Regulatory network contained 1301 nodes and 2527 connection pairs and that FOXA1 (forkhead box A1), BZRAP1-AS1 (benzodiazapine receptor associated protein 1 antisense RNA 1) and KRT8 (keratin 8) were the top three nodes of it. The enriched GO terms were mainly biological activity of the blood and cells-related. Total 29 DEGs (such as AGTR1, angiotensin II receptor, type 1) and 57 none-DEGs involved in the PPI network. Biological functions in blood circulation and the involved AGTR1 may play important roles in PC by gene-methylation. Besides, BZRAP1-AS1 may be novel biomarker related with PC.
目的是阐述前列腺癌的发病机制,并确定前列腺癌(PC)的潜在生物标志物。使用了包含8个前列腺癌转移灶和4个正常前列腺样本的DNA甲基化微阵列数据GSE38240以及包含6个前列腺原发性肿瘤和6个正常样本的基因表达谱数据GSE26910。筛选出PC的差异表达基因(DEGs)和差异甲基化位点,并与DEGs相关转录因子(TFs)构建调控网络。对获得的枢纽基因进行蛋白质-蛋白质相互作用网络分析。对下调的DEGs进行富集分析。共鉴定出351个DEGs,包括190个下调基因和161个上调基因以及3234个差异甲基化位点。共发现69个与DEGs相关的TFs。调控网络包含1301个节点和2527个连接对,其中叉头框A1(FOXA1)、苯二氮䓬受体相关蛋白1反义RNA 1(BZRAP1-AS1)和角蛋白8(KRT8)是前三个节点。富集的基因本体(GO)术语主要是血液和细胞相关的生物学活性。共有29个DEGs(如血管紧张素II受体1型AGTR1)和57个非DEGs参与蛋白质-蛋白质相互作用网络。血液循环中的生物学功能以及所涉及的AGTR1可能通过基因甲基化在PC中发挥重要作用。此外,BZRAP1-AS1可能是与PC相关的新型生物标志物。