基于生物信息学数据库探讨FOXO3基因在膀胱癌中的表达及临床意义  

Expression and clinical significance of FOXO3 gene in bladder cancer based on bioinformatics database

作　　者：陶燕[1] 李兰兰[1] 卢建中[1] 刘善辉 付生军[1] 张静[1] TAO Yan;LI Lanlan;LU Jianzhong;LIU Shanhui;FU Shengjun;ZHANG Jing(Key Laboratory of Urological Diseases in Gansu Province/Gansu Nephro-Urological Clinical Center,Lanzhou University Second Hospital,Lanzhou 730030,Gansu,China)

机构地区：[1]兰州大学第二医院,甘肃省泌尿系统疾病研究重点实验室/甘肃省泌尿系临床医学中心,甘肃兰州730030

出　　处：《癌变．畸变．突变》2020年第5期374-379,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：兰州大学第二医院“萃英科技创新”计划(CY2019-QN05)。

摘　　要：目的:探讨叉头转录蛋白O亚族3(FOXO3)基因在膀胱癌中的表达及临床意义。方法:利用GEPIA数据库分析FOXO3基因在膀胱癌与其癌旁正常组织中的表达情况,及其与患者预后的关系,利用UALCAN数据库分析膀胱癌中FOXO3表达与淋巴结转移的关系;通过TIMER数据库分析FOXO3基因表达与膀胱癌免疫浸润水平的相关性;通过String数据库分析与FOXO3相互作用的蛋白。结果:GEPIA数据库分析结果显示,FOXO3基因在膀胱癌组织中的表达显著低于癌旁正常组织(P<0.01);低表达FOXO3基因的患者总生存率(OS)和无疾病生存率(DFS)均显著高于高表达者(P<0.05)。UALCAN数据库分析结果显示膀胱癌中FOXO3的表达与淋巴结转移无明显相关。TIMER数据库分析显示FOXO3基因表达与B细胞(r=0.133,P<0.05)、CD8+T细胞(r=0.262,P<0.01)、CD4+T细胞(r=0.12,P<0.05)、巨噬细胞(r=0.252,P<0.01)、中性粒细胞(r=0.242,P<0.01)和树突状细胞(r=0.162,P<0.01)的免疫浸润水平呈正相关。蛋白相互作用网络分析发现,AKT1、SIRT1、EP300、BCL2L11、SOD2、SGK1、AKT2、CREBBP、CDKN1B、SMAD4等蛋白与FOXO3具有明显相互作用。结论:基于肿瘤基因数据库分析发现,FOXO3基因在膀胱癌组织中低表达,其高表达与患者预后不良相关;FOXO3表达与膀胱癌免疫细胞的浸润水平有关。OBJECTIVE:To use a bioinformatics database for determining expression levels and clinical significance of FOXO3 in bladder cancer(BLCA).METHODS:The GEPIA databases were used to analyze the expression of FOXO3 gene in bladder cancer and normal bladder tissues.In addition,the RNA-Seq data and clinical data were downloaded from the UALCAN database and were used to determine correlations between FOXO3 gene expression and prognosis.TIMER was used to investigate correlations between FOXO3 and cancer immune infiltrate cells.The String database was used to identify proteins which interact with FOXO3.RESUITS:Based on analyses of the GEPIA database,expression of FOXO3 gene in bladder cancer tissues was significantly lower than that in normal tissues(P<0.01).In addition,the low expression was significantly associated with longer and disease-free survival in patients than the high expression(all P<0.05).Analyses of the TIMER database show that the FOXO3 expression had a positive correlation with infiltrating levels of B cells(r=0.12,P<0.05),CD8+T cells(r=0.262,P<0.01),CD4+T cells(r=0.12,P<0.05),macrophages(r=0.252,P<0.01),neutrophils(r=0.242,P<0.01)and dendritic cells(r=0.162,P<0.01)in bladder cancers.Analyses of protein-protein interactions reveal that AKT1,SIRT1,EP300,BCL2L11,SOD2,SGK1,AKT2,CREBBP,CDKN1B and SMAD4 interacted with FOXO3.CONCLUSION:Our findings demonstrate that the FOXO3 gene was expressed at low levels in bladder cancer tissues.However,high FOXO3 expression was correlated with poor prognosis of bladder cancer and was correlated with infiltrating levels of immune cells in bladder cancer.

关 键 词：膀胱癌 FOXO3 数据库 表达 诊断 

分 类 号：R737.14[医药卫生—肿瘤]