基于生物信息学对头颈鳞癌的关键基因进行分析

Analysis of key genes in head and neck squamous cell carcinoma based on bioinformatics

目的探讨头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)潜在的关键基因。方法从GEO数据库中下载GSE6631和GSE13398芯片数据集,通过GEO2R工具筛选出HNSCC癌组织与正常组织的差异表达基因(differentially expressed genes,DEGs)。HNSCC高通量测序数据从TCGA数据库中下载,通过R包edgR筛选HNSCC癌组织与正常组织的DEGs。利用STRING数据库构建蛋白互作网络(protein-protein interaction network,PPI network)。关键基因通过Cytoscape软件及GEPIA在线工具进行筛选,并进行GO(Gene Ontology)功能注释分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集分析。最后通过QRT-PCR在临床标本上对关键基因表达进行验证。结果在本研究中,共筛选出70个DEGs,其中34个基因表达上调,36个基因表达下调。PPI网络中候选关键基因的功能分析显示大部分基因富集于细胞外基质组织、细胞外基质受体相互作用、黏着斑和PI3K-Akt信号通路等。MCC算法结合生存分析,最终确定7个关键基因:PLAU、FAP、LAMC2、SERPINH1、ITGA6、SPP1和MMP1。结论7个关键基因PLAU、FAP、LAMC2、SERPINH1、ITGA6、SPP1、MMP1可为HNSCC的诊断及治疗提供潜在靶点。

Objective To explore the potential key genes for head and neck squamous cell carcinoma(HNSCC).Methods The GSE6631 and GSE13398 microarrays were downloaded from the GEO database,and differentially expressed genes(DEGs)of HNSCC tissues and normal tissues were screened out by GEO2 R.HNSCC high-throughput sequencing data were downloaded from TCGA database.DEGs of HNSCC cancer tissues and normal tissues were screened by R package edgR.STRING database was used to construct the protein-protein interaction network(PPI network).Key genes were screened by Cytoscape software and GEPIA online tools,and GO(Gene Ontology)functional annotation analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis were performed.Finally,QRT-PCR was used to verify the expression of key genes in clinical specimens.Results In this study,a total of 70 DEGs were selected,among which 34 genes were up-regulated and 36 genes were down-regulated.Functional analysis of key candidate genes in PPI network showed that most of the genes were enriched in extracellular matrix tissues,extracellular matrix receptor interaction,adhesion spots and PI3 K-Akt signal transduction pathway.MCC algorithm combined with survival analysis finally identified 7 key genes:PLAU,FAP,LAMC2,SERPINH1,ITGA6,SPP1 and MMP1.Conclusion Seven key genes,PLAU,FAP,LAMC2,SERPINH1,ITGA6,SPP1 and MMP1,can provide potential targets for the diagnosis and treatment of HNSCC.