miR-218通过靶向调控Robo1对膀胱癌患者预后影响的生物信息学分析

Bioinformatics Analysis of the Effect of miR-218 Targeting Robo1 on the Prognosis of Bladder Cancer Patients

目的:探讨miR-218通过靶向调控Robo1对膀胱癌增殖和迁移的影响。方法:采用生物信息学筛选miR-218的靶基因并分析Robo1在膀胱癌中的表达及其突变情况。采用real-time PCR检测30例膀胱癌患者癌组织和癌旁组织中miR-218和Robo1表达水平。根据Robo1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:miR-218能与Robo1基因3’-UTR靶向结合,从而抑制Robo1基因的表达。Robo1在膀胱癌及多种肿瘤中表达水平变化不显著。Robo1基因主要突变形式为融合突变、扩增突变、深度缺失突变。Robo1相关基因蛋白网络中共有21个相关基因,基因间的联系为75,平均节点相关度为7.14,区域聚类指数为0.77,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、Rap1信号通路及cGMP-PKG信号通路等。DFS(HR=1.40,P=0.044)和OS(HR=1.40,P=0.037)在Robo1高表达组患者显著低于低表达组。结论:Robo1基因在肿瘤组织中呈现明显的突变,其高表达与膀胱癌患者的预后不良有关。miR-218靶向抑制Robo1表达为膀胱癌靶向治疗提供了新思路。

Objective:To investigate the effect of miR-218 on the proliferation and migration of bladder cancer by targeting Robo1.Methods:Bioinformatics was used to screen the target gene of miR-218,and the expression and mutation of Robo1 in bladder cancer were analyzed.Real time PCR was used to detect the expression of miR-218 and Robo1 in 30 cases of bladder cancer.According to the expression level of Robo1,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:miR-218 could bind to 3’-UTR of Robo1 gene and inhibit the expression of Robo1 gene.The expression level of Robo1 in bladder cancer and other tumors did not change significantly.The main mutations of Robo1 gene were fusion mutation,amplification mutation and deep deletion mutation.There were 21 related genes in the protein network of Robo1 related genes.The association between genes was 75,the average node correlation was 7.14,and the regional clustering index was 0.77.The correlation protein network was significantly enriched(P<0.001).KEGG signaling pathway is mainly enriched in Ras signaling pathway,Rap1 signaling pathway and cGMP PKG signaling pathway.DFS(HR=1.40,P=0.044)and OS(HR=1.40,P=0.037)in Robo1 high expression group were significantly lower than those in low expression group.Conclusion:The mutation of Robo1 gene is obvious in tumor tissues,and its high expression is related to the poor prognosis of bladder cancer patients.miR-218 targeted inhibition of Robo1 expression provides a new idea for targeted therapy of bladder cancer.