胃癌预后标志物circRNA-miRNA-mRNA的ceRNA网络生物信息学分析

Bioinformatics Analysis of circRNA-miRNA-mRNA ceRNA Network for Prognosis in Gastric Cancer

目的构建胃癌(gastric cancer,GC)中与预后相关的circRNA-miRNA-mRNA竞争性内源RNA(competing endogenous RNA,ceRNA)调控网络,探究诊治靶点。方法从GEO、TCGA数据库中获得GC中差异表达的circRNAs(circular RNA,circRNA)及相关miRNAs(microRNA,miRNA)、mRNAs,利用Cytoscape构建circRNA-miRNA-mRNA ceRNA网络,关注差异表达mRNAs功能,确定枢纽基因,最终通过Kaplan-Meier生存分析确定其预后价值。结果ceRNA网络由差异表达的2个circRNAs、5个miRNAs和349个mRNAs组成。功能富集分析提示差异mRNAs在“肌肉系统发育”、“金属离子跨膜转运蛋白活性”、“突触膜”和“钙信号通路”等方面和通路显著富集。构建了包含125个节点和165条边的PPI网络,并鉴定出10个枢纽基因,生存分析提示低ADAR1D或PTGFR表达可能导致GC患者预后不良。结论成功构建了与GC预后相关的circRNA-miRNA-mRNA ceRNA调控网络,确定了hsa_circ_0001190/hsa-miR-7-5p/ADRA1D和hsa_circ_0036287/hsa-miR-3127-5p/PTGFR两个在GC中具有潜在预后价值的轴,为GC的靶向诊治与研究提供新的依据。

Objective To construct a prognostic circRNA-miRNA-mRNA ceRNA network in gastric cancer(GC)and explore the diagnostic and therapeutic targets.Methods Differentially expressed circular RNAs(circRNA),related microRNAs(miRNA)and mRNAs in GC were obtained from GEO and TCGA databases.Cytoscape was utilized to construct the circRNA-miRNA-mRNA ceRNA network,to understand the biological functions of differentially expressed mRNAs and identifying the hub genes.Kaplan-Meier survival analysis was used to verify the prognostic values.Results The ceRNA network was consisted of 2 circRNAs,5 miRNAs and 349 mRNAs that were differentially expressed.Functional enrichment analysis revealed that mRNAs were significantly enriched in terms and pathways like“muscle system process”,“metal ion transmembrane transporter activity”,“synaptic membrane”and“calcium signaling pathway”.A PPI network containing 125 nodes and 165 edges was constructed and 10 hub genes were identified.Survival analysis implied that low ADAR1D or PTGFR expression levels might lead to poor prognosis of GC patients.Conclusion The circRNA-miRNA-mRNA ceRNA network involved in prognosis of GC is successfully constructed.Two axes,the hsa_circ_0001190/hsa-miR-7-5p/ADRA1D and the hsa_circ_0036287/hsa-miR-3127-5p/PTGFR,are identified with potential prognostic values in GC,providing a new target for diagnosis andtreatment of GC.