基于生物信息学方法分析肝癌和糖尿病共有的关键基因和信号通路

Bioinformatics Analysis of Common Key Genes and Signal Pathways in Liver Cancer and Diabetes

目的利用生物信息学方法探究肝癌和糖尿病共有的基因特征和致病机制。方法在GEO(Gene Expression Omnibus)数据库中下载肝癌数据集(GSE121248)和糖尿病数据集(GSE29221),通过R语言包进行差异分析,Venn图获取共有的差异表达基因(differentially expressed genes,DEGs)。对DEGs进行GO(gene ontology)和KEGG(kyoto encyclopedia of genes and genomes)富集分析,Cytoscape软件获取PPI(protein protein interaction)网络中的关键模块和核心基因。在NetworkAnalyst数据库中进行基因、转录因子和mi-RNA的网络互作分析。DGIdb数据库用于基因与药物的互作分析。通过Kaplan-Meier Plotter数据库分析核心基因的预后价值。结果共筛选出39个DEGs,这些DEGs在细胞外基质、胰岛素样生长因子受体信号通路的正调控、肝素结合和P53通路等信号通路中显著富集。共筛选出6个核心基因(THBS1、DCN、BGN、COL14A1、LUM、PCOLC),其中2个核心基因(DCN、THBS1)可与相关肿瘤治疗药物互作,1个核心基因(DCN)与肝癌患者预后相关。结论DCN可能是治疗糖尿病并发肝癌的潜在药物靶点。

Objective To explore the gene features and pathogenic mechanisms shared by hepatocellular carcinoma and diabetes mellitus using bioinformatics methods.Methods The hepatocellular carcinoma dataset(GSE121248)and diabetes mellitus dataset(GSE29221)were downloaded from the GEO(Gene Expression Omnibus)database,and were analyzed by R.Venn diagrams were used to obtain the shared differentially expressed genes(DEGs).GO(gene ontology)and KEGG(kyoto encyclopedia of genes and genomes)enrichment analyses were performed on DEGs,and Cytoscape software was used to obtain the key modules and core genes in the proteinprotein interaction(PPI)network.The network interaction analyses of genes,transcription factors and mi-RNAs were performed in NetworkAnalyst database.DGIdb database was used for gene-drug interaction analysis.The prognostic values of the core genes were analyzed by Kaplan-Meier Plotter database.Results A total of 39 DEGs were screened out,which were significantly enriched in pathways such as extracellular matrix,positive regulation of insulin-like growth factor receptor signaling pathway,heparin binding,and P53 signaling pathway.6 core genes(THBS1,DCN,BGN,COL14 A1,LUM and PCOLC)were screened out,of which two core genes(DCN and THBS1)could interacted with some tumor therapeutic agents and one core gene(DCN)was associated with the prognosis of hepatocellular carcinoma patients.Conclusion DCN may be a potential drug therapeutic target for patients with both diabetes and hepatocellular carcinoma.