摘要
目的:针对结直肠癌(colorectal cancer,CRC)预后的肿瘤标志物尚缺乏可靠的准确度和灵敏度。本研究旨在采用生物信息学方法,筛选并验证一组与CRC诊断与预后相关的基因。方法:从NCBI-GEO数据库中选取关于CRC和正常结直肠黏膜(colorectal mucosa,CRM)组织标本全RNA组测序数据集GSE31905、GSE35279和GSE41657,并分析其中的差异表达基因(differentially expressed genes,DEGs),先通过Venn图获取这3个数据集的共同DEGs,然后用STRING网络系统和Cytoscape软件进一步富集上述基因,最后在Kaplan-Meier plotter网站上验证富集后的基因与CRC预后的相关性。结果:通过NCBI-GEO数据库中自带的GEO2R工具分别筛选出3个数据集中CRC与CRM的DEGs(|log_(2)FC|>2和P<0.05)。用Venn图分析软件,将3个数据集中的上调/下调基因分别取交集,得出3个样本共105个共有的上调基因和140个共有的下调基因。将上述上调/下调基因导入STRING网络系统,得出相互作用的基因。将相互作用的基因集导入Cytoscape软件,用MCODE(Molecular Complex Detection)插件查找到61个上调基因。最后通过Kaplan-Meier plotter网站,得到EPHB2、KLK8、DIAPH3、STC2、OXTR、MMP7、MET、KRT85、KRT6B、KRT23、KLK10等11个在CRC中高表达的基因,且与预后相关。结论:通过生物信息学分析和验证,上述11个基因可在一定程度上预测CRC的不良预后,为CRC的诊断、治疗和预后提供可能的靶标。
Objective: The biomarkers targeting colorectal cancer(CRC) prognosis are short of high accuracy and sensitivity in clinic. Through bioinformatics analysis, we aim to identify and confirm a series of key genes referred to the diagnosis and prognosis of CRC.Methods: GSE31905, GSE35279, and GSE41657 were selected as complete RNA sequencing data sets of CRC and colorectal mucosa(CRM) tissues from the NCBI-GEO database, and the differentially expressed genes(DEGs) were analyzed. The common DEGs in these 3 data sets were obtained by Venn map, and enriched by STRING network system and Cytoscape software. The Kaplan-Meier plotter website was used to verify the correlation between the enriched genes and the prognosis of CRC.Results: For the whole RNA sequencing data sets of CRC and normal intestinal mucosa samples, the DEGs of CRC and CRM in the 3 data sets(|log_(2)FC| >2 and P<0.05) were screened by GEO2R tool in NCBI-GEO database. By using Venn graph analysis software,the intersection of up-regulated/down-regulated genes in 3 GSE datasets was obtained, and a total 105 up-regulated genes and 140 down-regulated genes were found in the 3 samples.The up-regulated/down-regulated genes were introduced into the STRING network system to obtain the interacting genes. The interacting gene sets were introduced into Cytoscape software, and 61 up-regulated genes were found by Molecular Complex Detection(MCODE) plug-in. Through the Kaplan-Meier plotter website, we found that EPHB2,KLK8, DIAPH3, STC2, OXTR, MMP7, MET, KRT85, KRT6B, KRT23, and KLK10 genes were highly expressed in CRC, and were related to the prognosis.Conclusion: The above 11 genes verified by bioinformatics retrieval and analysis can predict the poor prognosis of CRC to a certain extent, and they provide a possible target for the diagnosis and treatment of CRC.
作者
覃异
陈璐
陈立章
QIN Yi;CHEN Lu;CHEN Lizhang(Xiangya School of Public Health,Central South University,Changsha 410078;Department of Gastrointestinal Surgery,Xiangya Hospital,Central South University,Changsha 410008,China)
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2021年第10期1063-1070,共8页
Journal of Central South University ：Medical Science
关键词
生物信息学分析
RNA测序
结直肠癌
差异表达基因
bioinformatics analysis
RNA sequencing
colorectal cancer
different expressed genes
