可诱导神经生长因子过表达在进展期前列腺癌中的作用及其机制  

Study on nerve growth factor inducible overexpression in the progression of prostate cancer and its mechanism

作　　者：张小飞 胡建鹏[1] 薛博 徐旭 万远烨 吕玉梅 崔飞伦[1] Zhang Xiaofei;Hu Jianpeng;Xue Bo;Xu Xu;Wan Yuanye;Lyu Yumei;Cui Feilun(Department of Urology,the Affiliated People’s Hospital of Jiangsu University,Zhenjiang 212002,China;Department of Healthy Management Section,Zhenjiang College,Zhenjiang 212028,China)

机构地区：[1]江苏大学附属人民医院泌尿外科,镇江212002 [2]镇江市高等专科学校健康管理科,212028

出　　处：《中华实验外科杂志》2020年第8期1428-1430,共3页Chinese Journal of Experimental Surgery

基　　金：江苏省社会发展重点疾病研发计划项目(BE2016715);江苏省自然基金项目(BK20191221);江苏省医学重点人才项目(QNRC2016457);江苏省卫计委基金项目(H2017089)。

摘　　要：目的探讨可诱导神经生长因子(VGF)过表达在进展期前列腺癌(PCa)患者组织中的作用及其可能的分子生物学机制。方法应用肿瘤基因组图谱(TCGA)和GEO数据库下载PCa中VGF芯片数据进行分析;根据不同的临床病理参数评估VGF在PCa患者中的表达和甲基化水平;TCGA和GSE21032数据库下载VGF芯片数据并用Kaplan-Meier生存曲线分析其与PCa患者生存期的相关性;应用David及京都基金及基因组百科全书(KEGG)通路富集分析VGF在PCa中的作用机制,并用String系统构建PPI网络,应用Mcode plugin分析识别关键模块;PROMO系统预测VGF的潜在转录因子并进行回归分析。采用t检验。结果分析发现VGF mRNA在PCa中的表达上调,在GSE55945数据库中,PCa与正常组织中VGF相对表达水平分别为29.8、24.5(t=7.612,P<0.05),TCGA数据库中PCa与正常组织中VGF相对表达水平分别为25.5、15.6(t=4.712,P<0.05),而且VGF表达与其甲基化水平呈显著负相关;VGF在晚期PCa中明显高表达,其甲基化水平在晚期PCa中明显降低;分析显示VGF低表达PCa患者无进展生存期明显延长,VGF低甲基化患者无进展生存期明显缩短;分析显示VGF在PCa中通过GnRH、RIG-I样受体和丝裂原活化蛋白激酶(MAPK)等多种途径发挥调控作用;回归分析显示SP1、MAZ、NR3C1和环磷酸腺苷反应元件结合蛋白1(CREB1)是PCa中VGF表达的调节因子。结论VGF在PCa组织中高表达且表达强度与PCa进展明显相关。Objective To study the correlation between the expression level of nerve growth factor inducible(VGF)and clinical progress in patients with prostate cancer(PCa).Methods The date of VGF chip in PCa downloaded from the cancer genome atlas(TCGA)and gene expression omnibus(GEO)database were analyzed.The expression and methylation levels of VGF in PCa patients were evaluated according to different clinic opathological parameters.The data of VGF chip was download from TCGA and GSE21032 databases and using Kaplan-Meier survival curve to analyze the correlation with the survival of PCa patients.The mechanism of VGF in PCa was analyzed by David and Kyoto gene and genome encyclopedia(KEGG)pathway enrichment,using String system to build PPI network and using Mcode plugin to analyze and identify key modules.The PROMO system was used to predicts the potential transcription factors of VGF and performing regression analysis.Results Analysis showed that VGF mRNA expression was up-regulated in PCa,in the GSE55945 database,the relative expression level of VGF in PCa and normal tissue were 29.8,24.5(t=7.612,P<0.05),in the TCGA database,the relative expression level of VGF in PCa and normal tissue were 25.5,15.6(t=4.712,P<0.05),and its expression was significantly negatively correlated with the methylation level.VGF was highly expressed in advanced stage of PCa,and its methylation level was significantly reduced.Analysis showed that lower expression of VGF was correlated to longer progression free survival time in PCa patients and the PCa patients with lower methylation level had a significant shorter progression free survival time.VGF plays a regulatory role in PCa through many pathway ways like GnRH,RIG-I-like receptor,mitogen-activated protein kinase(MAPK)and so on.Regression analysis showed that SP1,MAZ,NR3C1 and cyclic adenosine monophosphate response element binding protein 1(CREB1)were identified as regulators of VGF expression in PCa.Conclusion VGF is highly expressed in PCA and its expression intensity is significantly rela

关 键 词：前列腺癌 神经生长因子 生存期 生物信息学分析 生物标志物 

分 类 号：R737.25[医药卫生—肿瘤]