He Zhaohui, Tang Fucai, Lu Zechao, Huang Yucong, Lei Hanqi, Li Zhibiao, Zeng Guohua
Department of Urology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University Guangzhou 510230, China.
First Clinical College of Guangzhou Medical University Guangzhou 510230, China.
Am J Transl Res. 2018 May 15;10(5):1444-1456. eCollection 2018.
The present study aimed to investigate the gene expression changes in prostate cancer (PC) and screen the hub genes and associated pathways of PC progression. The authors employed integrated analysis of GSE46602 downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases to identify 484 consensual differentially expressed genes (DEGs) in PC, when compared with adjacent normal tissue samples. Functional annotation and pathway analysis were performed. The protein-protein interaction (PPI) networks and module were constructed. RT-qPCR was used to validate the results in clinical PC samples. Survival analysis of hub genes was performed to explore their clinical value. GO analysis results revealed that DEGs were significantly enriched in negative regulation of nitrobenzene metabolic process, extracellular space and protein homodimerization activity. KEGG pathway analysis results revealed that DEGs were most significantly enriched in focal adhesion. The top 10 hub genes were identified to be hub genes from the PPI network, and the model revealed that these genes were enriched in various pathways, including neuroactive ligand-receptor interaction, p53 and glutathione metabolism signaling pathways. RT-qPCR results validated that expression levels of eight genes (PIK3R1, BIRC5, ITGB4, RRM2, TOP2A, ANXA1, LPAR1 and ITGB8) were consistent with the bioinformatics analysis. ITGB4 and RRM2 with genetic alterations exhibited association with a poorer survival rate, compared with those without alterations. These results revealed that PC-related genes and pathways have an important role in tumor expansion, metastasis and prognosis. In summary, these hub genes and related pathways may act as biomarkers or therapeutic targets for PC.
本研究旨在调查前列腺癌(PC)中的基因表达变化,并筛选PC进展的关键基因和相关通路。作者对从基因表达综合数据库(Gene Expression Omnibus)和癌症基因组图谱(The Cancer Genome Atlas)数据库下载的GSE46602进行综合分析,以鉴定与相邻正常组织样本相比,PC中484个一致的差异表达基因(DEG)。进行了功能注释和通路分析。构建了蛋白质-蛋白质相互作用(PPI)网络和模块。使用RT-qPCR在临床PC样本中验证结果。对关键基因进行生存分析以探索其临床价值。基因本体(GO)分析结果显示,DEG在硝基苯代谢过程的负调控、细胞外空间和蛋白质同二聚化活性中显著富集。京都基因与基因组百科全书(KEGG)通路分析结果显示,DEG在粘着斑中最显著富集。从PPI网络中鉴定出前10个关键基因,该模型显示这些基因在各种通路中富集,包括神经活性配体-受体相互作用、p53和谷胱甘肽代谢信号通路。RT-qPCR结果验证了8个基因(PIK3R1、BIRC5、ITGB4、RRM2、TOP2A、ANXA1、LPAR1和ITGB8)的表达水平与生物信息学分析一致。与无基因改变的患者相比,发生基因改变的ITGB4和RRM2与较差的生存率相关。这些结果表明,PC相关基因和通路在肿瘤扩展、转移和预后中具有重要作用。总之,这些关键基因和相关通路可能作为PC的生物标志物或治疗靶点。