基于生物信息学分析筛选与鉴定结直肠癌的关键生物标志物  

Identification of hub genes as diagnostic and prognostic biomarkers for colorectal cancer using integrating bioinformatics analysis

作　　者：杨铁成 方效昌 窦婷亭 王华桥 杨丽洁 石丽稳 王丹雯 李炫飞 谢伟[1] Yang Tiecheng;Fang Xiaochang;Dou Tingting;Wang Huaqiao;Yang Lijie;Shi Liwen;Wang Danwen;Li Xuanfei;Xie Wei(Department of Gastrointestinal Surgery,Zhongnan Hospital of Wuhan University,Clinical Medical Research Center of Peritoneal Cancer of Wuhan,Clinical Cancer Study Center of Hubei Provence,Key Laboratory of Tumor Biological Behavior of Hubei Provence,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院胃肠外科,武汉市腹膜癌临床医学研究中心,湖北省肿瘤医学临床研究中心,肿瘤生物学行为湖北省重点实验室,430071

出　　处：《中华实验外科杂志》2021年第9期1775-1777,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(81770283);湖北省自然科学基金青年项目(2019CFB109);武汉市腹膜癌临床医学研究中心资助项目(2015060911020462);武汉大学中南医院创新培育基金(znpy2018004)。

摘　　要：目的通过生物信息学分析结直肠癌组织与正常癌旁组织的基因表达数据集,筛选出参与并影响结直肠癌发生发展的关键差异表达基因。方法从基因表达谱(GEO)数据库中下载3个结直肠癌组织信使RNA(mRNA)芯片数据集,为数据集GSE35279,数据集GSE50746和数据集GSE87211,共包括173个正常癌旁组织和297个结直肠癌组织。进行分析筛选,获得差异表达基因(DEGs)。使用标注可视化和集成发现数据库(DAVID)用于富集分析。通过STRING和Cytoscape数据库构建蛋白与蛋白相互作用网络,并得到关键DEGs。利用UALCAN、基因表达谱动态分析(GEPIA)等数据库分析关键基因的表达和生存分析,使用Log-rank检验方法。结果在结直肠癌和正常癌旁组织中共识别出212个DEGs和10个核心基因。GEPIA总生存期曲线显示,金属蛋白酶抑制剂-1(TIMP1)、分泌型磷蛋白1(SPP1)、蜗牛家族转录抑制因子1 (SNAI1)和胰高血糖素(GCG)的表达水平与结直肠癌患者总体生存率有关。高表达组TIMP1、SPP1和SNAI1结直肠癌患者总体生存率分别显著低于低表达组患者,并且低表达组GCG结直肠癌患者总体生存率显著低于高表达组患者,其结果具有统计学意义(P<0.05)。结论筛选出4个结直肠癌临床诊断和预后的生物标志物,为进一步研究结直肠癌发病分子机制以及早期诊断和预后提供基础依据。Objective To analyze gene expression datasets from colorectal cancer and adjacent normal colorectal tissues to identify key differentially expressed genes that are involved in the development and progression of colorectal cancer.Methods Three mRNA microarray datasets were downloaded from GEO database,GSE35279,GSE50746 and GSE87211,comprising 173 normal adjacent tissues and 297 colorectal cancer tissues.The DEGs were obtained by screening and analysis.Functional enrichment analysis was performed using DAVID database.Protein-protein interaction network was constructed by STRING and Cytoscape.Subsequently,key DEGs were obtained.Expression and survival analysis of key genes were analyzed using UALCAN and GEPIA databases.The Log-rank test was used for survival difference analysis.Results A total of 212 DEGs and 10 hub genes were screened.The total survival curve of GEPIA showed that the expression levels of TIMP1,SPP1,SNAI1 and GCG were related to the overall survival rate of colorectal cancer patients.The overall survival rates in high expression group of TIMP1,SPP1 and SNAI1 were significantly lower than those in low expression group,and the overall survival rates of in low GCG expression group were significantly lower than those in high expression group(P<0.05).Conclusion Four biomarkers of clinical diagnosis and prognosis of colorectal cancer were selected to provide basis for further study of molecular mechanism of colorectal cancer and early diagnosis and prognosis.

关 键 词：结直肠癌 生物信息学 

分 类 号：R735.34[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]