摘要
目的胃癌是一种常见的消化道恶性肿瘤,多个基因和miRNA参与了胃癌的发生、发展和转移。本研究选取胃癌相关的mRNA和miRNA表达数据,利用生物信息学方法构建胃癌相关的mRNA-miRNA融合网络并识别胃癌相关的关键基因。方法从基因表达综合数据库(Gene Expression Omnibus,GEO)中选取胃癌相关的mRNA(GSE54129)和miRNA(GSE23739)表达数据,利用GEO2R筛选出差异表达mRNA和miRNA,利用STRING数据库和DAVID软件进行网络构建和功能富集分析,应用Cytoscape软件进行网络拓扑结构分析,应用TFcheckpoint数据库识别网络中的转录因子,应用Kaplan-Meier ploter进行生存分析。结果共计识别出704个差异表达的mRNA和38个差异表达的miRNA。构建的mRNA和miRNA融合网络包含了71个基因、15个miRNA和145条边。这些基因主要富集到RNA聚合酶Ⅱ启动子转录调控、细胞黏附、细胞外空间(基质和胞外囊泡)和肝素结合等(经Benjamini校正后均P<0.05)。通过网络拓扑学结构分析识别出了14个胃癌相关的关键节点,其中包含CTNNB1、IGF1、THBS1、PTGS2、ACTA2、CTGF和APOE 7个基因,hsa-miR-375、hsa-miR-107、hsa-miR-199a-3p、hsa-miR-513a-5p和hsa-miR-146b-5p 5个miRNA,SOX2和GATA62个转录调控因子。针对以上7个基因和2个转录调控因子的生存分析证实这些节点均与胃癌患者的生存曲线有关联,均P<0.05。结论胃癌的发生与发展受到涉及多个基因、miRNA和其他转录因子的生物分子网络调控,其关键节点对胃癌预后的预测有重要临床意义。
OBJECTIVE Gastric cancer is a common malignant tumor of gastrointestinal tract.Multiple genes and miRNAs are involved in its occurrence,development and metastasis.METHODS In this study,we chose gastric related mRNA(GSE54129)and miRNA(GSE23739)expression data from Gene Expression Omnibus(GEO)database.GEO2 R was used to select differential expressed mRNA and miRNA.STRING database and DAVID software were used to do the network construction and functional enrichment analysis.Cytoscape software was used to analyze the network topological structure.TF checkpoint was used to identify the transcription factor.Kaplan-Meier ploter was used to do the survival analysis.RESULTS There were 704 differential expressed mRNAs and 38 differential expressed miRNAs.The gastric related mRNA-miRNAs fusion network consisted of 71 genes,15 miRNAs and 145 edges.These genes were enriched in regulation of transcription from RNA polymeraseⅡpromoter,cell adhesion,extracellular space(extracellular matrix and extracellular vesicles)and heparin binding et al(Benjamini adjusted P<0.05).Fourteen key nodes were identified by network topological analysis including 7 genes,5 miRNAs and 2 transcription factors.They were the CTNNB1,IGF1,THBS1,PTGS2,ACTA2,CTGF,APOE,hsa-miR-375,hsa-miR-107,hsa-miR-199 a-3 p,hsa-miR-513 a-5 p,hsa-miR-146 b-5 p,SOX2 and GATA 6.Survival analysis of the above 7 genes and 2 transcription factors confirmed that these nodes were significantly correlated with the survival curves of gastric cancer patients(P<0.05).CONCLUSIONS This study demonstrated that the occurrence and development of the gastric cancer was regulated by a biological molecular network involving many genes,miRNAs and transcription factors,the key nodes had important clinical significance in predicting the prognosis of gastric cancer.
作者
赵小蕾
陈应坚
廖苑君
修良昌
覃继恒
饶绍奇
ZHAO Xiao-lei;CHEN Ying-jian;LIAO Yuan-jun;XIU Liang-chang;QIN Ji-heng;RAO Shao-qi(Institute for Medical Systems Biology,Guangdong Medical Unviersity,Dongguan 523808,P.R.China;School of Public Health,Guangdong Medical Unviersity,Dongguan 523808,P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2020年第8期612-618,共7页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81373085)
广东医科大学基金(M2014010)。
