摘要
目的 采用4个芯片数据集来挖掘结直肠癌差异基因,通过基因注释和蛋白相互作用网络构建找到关键基因。方法 下载GEO芯片数据GSE4398、GSE21815、GSE32323、GSE44076,筛选结直肠癌和正常组织间差异表达的基因,采用R3.4.4软件进行数据处理和分析,通过取交集获得候选的差异基因,通过Funrich软件进行基因功能分析,通过String和Cytoscape软件进行基因编码蛋白的相互作用分析。结果 通过差异基因分析并取4个GEO数据集的交集,一共获得430个差异表达基因,其中表达上调的基因277个,表达下调的基因153个。基因富集分析发现,表达上调的基因主要位于细胞核、细胞浆、微管、中心体和细胞外;主要参与纺锤体组装;主要参与调节趋化因子活性,在细胞周期、有丝分裂G1-G1/S期、M-M/G1期、G2/M期、DNA破坏关键节点及DNA复制等信号通路中富集。153个表达下调的基因主要富集在细胞外、参与代谢过程,发挥的分子功能主要是催化活性和配体依赖性核受体活性,下调基因没有富集在某条信号通路上。通过蛋白互作网络初步鉴定了CDK1、CCNB1、TOP2A、MAD2L1、TTK、BUB1B、AURKA、RRM2、UBE2C、ASPM等结直肠癌相关的关键基因。结论 通过基因芯片结合生物信息学方法,发现了结直肠癌相关的关键基因,有助于明确结直肠癌发病的分子机制,这些关键基因也可作为结直肠癌的治疗靶点。
Objective To integrate four microarray sets to screen differentially expressed genes and to find key genes with gene annotation and protein-protein interaction network construction. Methods Datasets were download from GSE4398,GSE21815,GSE32323,GSE44076,data processing and analysis process were done with R3.4.4 software,the differentially expressed genes overlaps were outputted,gene function analysis were completed with Funrich software,further protein-protein interaction were done with String and Cytoscape software. Results A total of 430 differentially expressed genes were obtained by differential gene analysis with overlaps of four GEO datasets,of which 277 genes were up-regulated and 153 genes were down-regulated.Up-regulated genes were mainly enriched in the nucleus and cytoplasm,tubes,central body and cells;mainly involved in spindle assembly;mainly involved in regulating chemokine activity,cell cycle G1-G1/S phase and mitosis,M-M/G1 and G2/M phase,DNA damage checkpoint and DNA replication signaling pathway.The down-regulated genes were mainly concentrated in the extracellular and involved in the metabolic process,and their molecular functions were mainly catalytic activity and ligand-dependent nuclear receptor activity.The down-regulated genes were not concentrated in a certain signaling pathway.CDK1,CCNB1,TOP2A,MAD2L1,TTK,BUB1B,AURKA,RRM2,UBE2C,ASPM were identified as key genes related to colorectal cancer by protein interaction network. Conclusion The key genes of colorectal cancer can be obtained by the combination of genechip and bioinformatics analysis,which can help us determining the potential molecular mechanism of colorectal cancer,These candidate genes also can be used as therapeutic targets for colorectal cancer.
作者
朱义芳
戴红梅
张峪涵
魏丹凤
潘逼然
刘蕾
张彤彤
郭元彪
刘华伟
ZHU Yifang;DAI Hongmei;ZHANG Yuhan;WEI Danfeng;PAN Biran;LIU Lei;ZHANG Tongtong;GUO Yuanbiao;LIU Huawei(Department of Clinical Laboratory,Sichuan Provincial Orthopedic Hospital,Chengdu,Sichuan 610041,China;Department of Clinical Laboratory,the Second Affiliated Clinical College of Chongqing Medical University/the Third People′s Hospital of Chengdu,Chengdu,Sichuan 610031,China;Department of Neurology,the Second Affiliated Clinical College of Chongqing Medical University/the Third People′s Hospital of Chengdu,Chengdu,Sichuan 610031,China;Medical Research Center,the Second Affiliated Clinical College of Chongqing Medical University/the Third People′s Hospital of Chengdu,Chengdu,Sichuan 610031,China)
出处
《国际检验医学杂志》
CAS
2019年第14期1721-1725,共5页
International Journal of Laboratory Medicine
基金
成都市科技局科研项目(2018-YF05-00669-SN)
成都市卫健委科研项目(2018056,2018069,2016005)
四川省卫健委科研项目(18PJ126,18PJ112)