Slit2在膀胱癌中的表达、信号通路及其与患者预后关系的生物信息分析

Expression and signal pathway of Slit2 in bladder cancer and its relationship with prognosis

[目的]探讨Slit2在膀胱癌中的表达及其与患者预后关系。[方法]采用生物信息学方法,在GTEx数据库中检索Slit2基因在人体各种组织中的表达水平,在TCGA数据库中分析Slit2多种肿瘤组织及在膀胱癌中的表达。采用在线分析工具cBioPortal,分析Slit2基因突变情况。根据Slit2表达水平,分为高、低表达组,比较两组患者无疾病进展生存(DFS)和总生存(OS)是否存在差异。[结果]Slit2基因mRNA在膀胱癌患者癌组织中的表达水平明显高于癌旁正常膀胱组织(P<0.05),且Slit2表达水平与患者临床分期有关,分期越高表达水平越高(P<0.05)。Slit2基因主要突变形式为融合突变、扩增突变、深度缺失突变和多重突变等。其中缺失突变占25.55%,同义突变占8.19%,无意义突变占2.01%。单核苷酸突变主要类型为C>T(28.51%)、G>T(13.64%)和C>A(9.85%)。STRING数据库中构建Slit2相关基因蛋白网络,网络中共有21个相关基因,基因间的联系为92,平均节点相关度为8.76,区域聚类指数为0.776,相关蛋白网络富集明显(P<0.001)。蛋白网络相关基因KEGG信号通路主要富集于Ras信号通路、T细胞受体信号通路、Rap1信号通路和ErbB信号通路等。Slit2高低表达膀胱癌患者无疾病进展生存(DFS)和总生存(OS)间均存在明显的差异(P<0.05)。无疾病进展生存(DFS)(HR=1.5,P=0.026)和总生存(OS)(HR=1.50,P=0.015),在Slit2高表达组患者显著低于低表达组,提示Slit2高表达是膀胱癌预后不良的因素。[结论]Slit2基因在膀胱癌患者癌组织中表达水平明显上调,高表达与膀胱癌患者的预后不良有关。

[Objective]To investigate the expression of Slit2 in bladder cancer and its relationship with,prognosis.[Methods]The expression levels of Slit2 gene in various human tissues were retrieved from GTEX database by bioinformatics.The expression of Slit2 in bladder cancer was analyzed in TCGA database.The Slit2 gene mutation was analyzed by cbioportal.According to the expression level of Slit2,the patients were divided into high and low expression groups,and the differences of disease-free survival(DFS)and overall survival(OS)between the two groups were compared.[Results]The expression level of Slit2 mRNA in bladder cancer tissues was significantly higher than that in adjacent normal bladder tissues(P<0.05),and the expression level of Slit2 was related to the clinical stage of patients,the higher the stage,the higher the expression level(P<0.05).The main mutations of Slit2 gene were fusion mutation,amplification mutation,deep deletion mutation and multiple mutation.Among them,deletion mutation accounted for 25.55%,synonymous mutation accounted for 8.19%,nonsense mutation accounted for 2.01%.The main types of SNPs were C>T(28.51%),G>T(13.64%)and C>A(9.85%).There were 21 related genes in the network,the association between genes was 92,the average node correlation was 8.76,the regional clustering index was 0.776,and the correlation protein network was significantly enriched(P<0.001).KEGG signaling pathway is mainly enriched in Ras signaling pathway,T cell receptor signaling pathway,Rap1 signaling pathway and erbB signaling pathway.There were significant differences in disease-free survival(DFS)and overall survival(OS)in bladder cancer patients with high and low expression of Slit2(P<0.05).Progression free survival(DFS)(HR=1.5,P=0.026)and overall survival(OS)(HR=1.50,P=0.015)were significantly lower in patients with high expression of Slit2 than those in patients with low expression of Slit2,suggesting that high expression of Slit2 is a poor prognostic factor for bladder cancer.[Conclusion]The expression level of Slit2 gene is significantly up-regulated in bladder cancer,and its high expression is associated with poor prognosis of bladder cancer patients.