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前列腺癌潜在生物标志物的综合生物信息学分析

Integrated Bioinformatics Analysis of Potential Biomarkers for Prostate Cancer.

作者信息

Tan Jiufeng, Jin Xuefei, Wang Kaichen

机构信息

Department of urology, China-Japan Union Hospital of Jilin University, 126 Xiantai ST, Changchun, Jilin Province, 130033, China.

出版信息

Pathol Oncol Res. 2019 Apr;25(2):455-460. doi: 10.1007/s12253-017-0346-8. Epub 2017 Dec 19.

Abstract

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.

摘要

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。

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