基于GEO数据库对胆管癌潜在分子靶点的筛选及生物信息学分析

背景胆管癌恶性程度高,预后差.靶向治疗是胆管癌的重要研究方向,探索新的分子靶点对于胆管癌靶向治疗至关重要.目的用生物信息学分析方法挖掘胆管癌的枢纽基因,为胆管癌的靶向治疗提供潜在分子靶点.方法从GEO数据库中下载2组胆管癌表达谱芯片数据,采用GEO2R在线分析工具筛选胆管癌肿瘤组织与正常组织差异表达基因,对差异表达基因作GO富集分析、KEGG通路分析、蛋白质相互作用网络分析,利用Cytoscape软件筛选枢纽基因.使用GEPIA数据库对枢纽基因在胆管癌组织中的表达量进行验证.结果共得到共同差异表达基因158个.GO富集分析结果显示,差异基因主要参与细胞对锌离子反应、细胞增殖与粘附、代谢以及蛋白质聚合等生物学过程,主要存在外泌体、胞外区、弹性纤维等区域,主要分子功能与结合肝素、半胱氨酸型内肽酶抑制剂活性、蛋白质同源二聚化、受体结合及磷酸吡哆醛结合等相关.KEGG通路分析结果显示,差异基因主要参与矿物质吸收、代谢、PPAR信号通路及脂肪酸降解等过程.基于String数据库构建蛋白质相互作用网络图,Cytoscape软件CytoHubba插件筛选枢纽基因,皆为上调基因.GEPIA数据库验证枢纽基因在胆管癌组织中表达量显著高于正常组织.结论本研究获取了8个与胆管癌相关的枢纽基因,分别是NUSAP1,TOP2A,RAD51AP1,MCM4,KIAA0101,CDCA5,TYMS,ZWINT.这些基因为深入研究胆管癌的靶向治疗提供了新思路,有望成为新的分子治疗靶点.

Potential molecular target screening and bioinformatics analysis of cholangiocarcinoma based on GEO database

BACKGROUND Cholangiocarcinoma is a highly malignant tumor with a poor prognosis.Targeted therapy is important for the treatment of cholangiocarcinoma,and it is therefore of great clinical importance to identify novel molecular targets for targeted therapy of this malignancy.AIM To identify potential molecular targets for the treatment of cholangiocarcinoma and identify the key genes involved in cholangiocarcinoma by bioinformatics analysis.METHODS We downloaded two sets of cholangiocarcinoma expression profile data from GEO database.GEO2R online analysis tool was used to screen differentially expressed genes in cholangiocarcinoma tumor tissues and normal tissues,and we performed GO enrichment analysis,KEGG pathway analysis,and protein interaction network for differentially expressed genes.We used Cytoscape software to calculate key genes.The GEPIA database was used to verify the expression of hub genes in cholangiocarcinoma tissues.RESULTS A total of 158 differentially expressed genes were identified.GO enrichment analysis showed that these differential genes were mainly involved in the cellular response to zinc ion,negative regulation of growth,cell adhesion,metabolic process,and protein homotetramerization.They were enriched in exosomes,extracellular spaces,elastic fibers,and organelle membranes.The main molecular functions are related to heparin binding,cysteine-type endopeptidase inhibitor activity,protein homodimerization activity,receptor binding,and pyridoxal phosphate binding.KEGG pathway analysis showed that differential genes are mainly involved in processes such as mineral absorption,carbon and propanoate metabolism,PPAR signaling pathway,and fatty acid degradation.A protein interaction network diagram was constructed based on the String database,and the CytoHubba plug-in of the Cytoscape software was used to calculate the key genes.The key genes were all up-regulated ones.GEPIA analysis verified that the expression of key genes in cholangiocarcinoma tissues was significantly higher than that in normal tissues.CONCLUSION In this study,eight key genes related to cholangiocarcinoma were identified,including NUSAP1,TOP2A,RAD51AP1,MCM4,KIAA0101,CDCA5,TYMS,and ZWINT.These genes provide new ideas for in-depth study of the targeted therapy of cholangiocarcinoma,and are expected to become new molecular therapeutic targets.