摘要
目的:探讨叉头盒状O转录因子3(FoxO3)在膀胱癌中表达、相关生物学功能和信号通路以及与患者生存期的关系。方法:分析癌症基因组图谱数据库(TCGA)中膀胱癌患者的癌组织和正常膀胱组织中FoxO3基因表达水平。STRING数据库构建FoxO3基因相关蛋白-蛋白相互作用网络,对网络中的基因进行聚类分析,并采用cytoscape筛选网络中的关键基因。采用基因本体论(GO)和京都基因与基因组百科全书(KEGG)对FoxO3和相关基因进行功能富集。Cox回归模型构建生存曲线,比较FoxO3高低表达组患者的总生存期(OS)和无疾病进展生存期(DFS)有无差异。结果:FoxO3表达水平在膀胱癌组织中表达水平显著低于对应的正常膀胱组织(P<0.05),而FoxO3表达水平在不同临床分期膀胱癌患者的癌组织中无明显差异(P>0.05)。FoxO3蛋白-蛋白相互作用网络中共有51个蛋白和587个相互作用关,各蛋白平均相互作用指数为23,网络中各个蛋白富集明显(P<1-16)。FoxO3基因表达与FoxO3B基因表达呈正相关(r=0.94,P<0.05),而与TIMM16基因表达呈负相关(r=–0.43,P<0.05)。FoxO3低表达组膀胱癌患者的总生存期(HR=1.4,P=0.029)和无疾病进展生存期(HR=1.5, P=0.015)显著高于高表达组。结论:FoxO3在膀胱癌患者肿瘤组织中表达水平明显下调,且FoxO3低表达与患者的预后不良有关。
Objective To investigate the expression of Forkhead box protein O 3(FoxO3)in bladder cancer,its related biological functions and signaling pathwaysand its relationship with patient survival.Methods The expression level of FoxO3 gene in bladder cancer tissues and adjacent normal bladder tissues were analyzed in TCGA database.STRING database was used to construct the FoxO3 gene-related protein-protein interaction network,cluster analysis of the genes in the network,and Cytoscape was used to screen the key genes in the network.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to enrich the functions of FoxO3 and related genes.Cox regression model was used to construct survival curve and to compare the difference of total survival and disease-free survival between high and low FoxO3 expression groups.Results The expression level of FoxO3 gene in bladder cancer tissues was significantly lower than that in corresponding normal bladder tissues(P<0.05),while the expression level of FoxO3 gene in different clinical stages of bladder cancer tissues had no significant difference(P>0.05).There were 51 protein-protein interaction correlations and 587 protein-protein interaction correlations in the FoxO3 protein-protein interaction network.The average interaction index of each protein was 23,and the protein concentration in the network was obvious(P<1-16).FoxO3 gene expression was positively correlated with FoxO3B gene expression(r=0.94,P<0.05),but negatively correlated with TIMM16 gene expression(r=–0.43,P<0.05).The total survival time(HR=1.4,P=0.029)and disease-free progression survival(HR=1.5,P=0.015)of bladder cancer patients in FoxO3 low expression group were significantly higher than those in high expression group.Conclusion The expression of FoxO3 in bladder cancer tissues is significantly down-regulated,and the low expression of FoxO3 is associated with poor prognosis of bladder cancer patients.
作者
王德鑫
齐峰
刘一鸣
WANG De-xin;QI Feng;LIU Yi-ming(Department of Urology,Beichen Hospital of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin(300400),China)
出处
《中国中西医结合外科杂志》
CAS
2020年第3期435-440,共6页
Chinese Journal of Surgery of Integrated Traditional and Western Medicine
