首页|基于加权基因共表达网络分析筛选结直肠癌潜在的生物标志物

基于加权基因共表达网络分析筛选结直肠癌潜在的生物标志物

扫码查看
目的:通过加权基因共表达网络分析筛选结直肠癌(Colorectal cancer,CRC)潜在的生物标志物.方法:下载基因表达综合数据库(Gene expression omnibus,GEO)中的基因表达谱GSE44076 和GSE21815,使用R语言软件limma包和sva包筛选出CRC组和正常对照组中的差异表达基因(Differentially expressed genes,DEGs).采用加权基因共表达网络分析方法(Weighted gene co-expression network analysis,WGCNA)确定关联最强的基因模块.将模块中的基因与DEGs取交集,得到差异共表达基因.采用Metascape在线工具对差异共表达基因进行富集分析;在String数据库中构建蛋白-蛋白互作网络(Protein-protein interaction,PPI),导入Cytoscape软件中使用度值(Degree)方法筛选前 10 个连接度高的基因作为关键基因.在GEPIA数据库中对关键基因进行差异表达和生存分析验证.采用受试者操作特性(Receiver operating characteristic curve,ROC)曲线评估关键基因诊断价值.采用RT-qPCR检测关键基因在结直肠癌组织和癌旁组织中的表达水平.结果:GSE44076 和GSE21815 合并后的数据集共筛选 925 个DEGs,基于WGCNA获取关键模块基因 110 个,两者取交集共筛选出 86 个差异共表达基因.GO富集分析提示差异共表达基因主要富集于细胞核染色质、核基质、有丝分裂细胞周期过程、胞质分裂、染色体结构 DNA 代谢过程及调节和 DNA 复制等过程.KEGG 通路富集分析筛选出 BUB1、CDK1、TOP2A、NUF2、CEP55、MAD2L1、TPX2、AURKA、UBE2C、KIF4A共 10 个关键基因.经GEPIA数据库分析结果显示,关键基因在结直肠癌中都高表达,并且BUB1、MAD2L1 和AURKA与结直肠癌预后相关;CDK1 和MAD2L1 与临床分期相关,并且 ROC 曲线显示 CDK1 和 MAD2L1 具有良好的诊断效能.RT-qPCR 结果显示,MAD2L1、CDK1、BUB1 和AURKA在结直肠癌组织中显著上调.结论:关键基因MAD2L1、CDK1、BUB1 和AURKA参与结直肠癌的发生发展,可作为结直肠癌潜在的生物标志物.
Screening potential biomarkers for colorectal cancer based on weighted gene co-expression network analysis
Objective:Screening potential biomarkers for colorectal cancer(CRC)by weighted gene co-expression network analysis.Methods:The limma and sva programs were used to screen the differential expression genes(DEGs)in the CRC group and normal control group.The gene expression data sets GSE44076 and GSE21815 were obtained from the GEO database.Through the use of the WGCNA,the most stable gene clusters were identified.Genes that were differentially co-expressed were obtained by intersecting the module's genes with DEGs.Genes showing varied co-expression were analyzed for enrichment using the Metascape web tool.The protein-protein interaction network(PPI)was constructed using the string database,and Cytoscape software was employed to calculate the degree value,which was then used to identify the top 10 highly connected genes as important genes.Key genes were subjected to survival analysis and differential expression in the GEPIA database.Key gene diagnostic value was assessed using ROC curves.Clinical colorectal cancer tissues and adjacent tissues were analyzed for key gene expression levels using RT-qPCR.Results:The combined datasets of GSE44076 and GSE21815 yielded 925 differentially expressed genes,110 major module genes were derived using WGCNA,and 86 differently co-expressed genes were screened at the junction of the two.Post-enrichment analysis indicated that differentially expressed genes were mainly concentrated in chromatin,nuclear matrix,mitotic cell cycle,cytoplasmic division,DNA metabolism and regulation of chromosome structure,and DNA replication.KEGG pathway enrichment analysis screened a total of 10 key genes,including BUB1,CDK1,TOP2A,NUF2,CEP55,MAD2L1,TPX2,AURKA,UBE2C,and KIF4A.The results of GEPIA database analysis showed that key genes were highly expressed in colorectal cancer,and BUB1,MAD2L1 and AURKA were correlated with the prognosis of colorectal cancer.CDK1 and MAD2L1 were correlated with clinical stage,and the ROC curve showed that CDK1 and MAD2L1 had good diagnostic efficacy.RT-qPCR results showed that MAD2L1,CDK1,BUB1 and AURKA were significantly upregulated in colorectal cancer tissues.Conclusion:The important genes MAD2L1,CDK1,BUB1,and AURKA are implicated in the development of colorectal cancer and may serve as biomarkers for the disease.

Differentially expressed geneWeighted gene coexpression networkColorectal cancer

刘萌萌

展开 >

河南中医药大学第三附属医院病理科,河南 郑州 450000

差异表达基因 加权基因共表达网络 结直肠癌

2024

四川生理科学杂志
四川省生理科学会

四川生理科学杂志

影响因子:0.575
ISSN:1671-3885
年,卷(期):2024.46(10)