【摘要】 目的利用生物信息技术探讨喉癌的发生机制,寻找用于喉癌诊断和治疗的关键基因。方法本研究从基因表达综合数据库(Gene Expression Omnibus,GEO)下载基因芯片数据集GSE51985和GSE59102,筛选差异表达基因,并进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)功能富集分析,使用STRING在线数据库构建蛋白质-蛋白质相互作用网络(PPI),并利用Cytoscape进行了模块分析,筛选关键基因。然后用Oncomine数据库对关键基因进行泛癌分析,从癌症和肿瘤基因图谱数据库(The Cancer Genome Atlas, TCGA)下载喉癌相关基因表达数据和临床资料,对关键基因进行基因表达差异和生存分析。结果共筛选出差异基因218个。KEGG途径分析显示,差异基因主要富集于唾液分泌、ECM受体相互作用、细胞周期等途径。利用Cystoscape软件筛选关键基因,筛选出CHEK1、SERPINE1、SPP1、COL1A1、FOXM1、MMP9、CXCL12和MMP1共8个基因为关键基因。将关键基因输入GEPIA数据库寻找相似基因,将所有基因输入Metascape进行富集分析,主要富集于细胞外组织结构、PID整合素1途径、有丝分裂染色体分离等。利用TCGA数据库数据进行关键基因在喉癌组织与正常组织表达差异分析,8个关键基因差异均有统计学意义,在生存分析中,笔者发现COL1A1和MMP1的表达与喉癌总生存率显著相关。结论本研究中发现的差异基因和关键基因有助于深入了解喉癌发生、发展的分子机制,为喉癌的诊断和治疗提供新的候选靶点。更多还原

【Abstract】 Objective To explore the mechanism of laryngeal cancer by using bioinformatics and to find the key genes for diagnosis and treatment of laryngeal cancer. Methods In this study, gene chip datasets GSE51985 and GSE59102 were downloaded from Gene Expression Omnibus(GEO) to screen differentially expressed genes, and functional enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of genes and genomes(KEGG) was carried out. The protein-protein interaction network(PPI) was constructed by using STRING online database, and the key genes were screened by using the module analysis of Cytoscape. Then, Oncomine database was used for pan-cancer analysis of key genes, and the gene expression data and clinical data related to laryngeal cancer were downloaded from the Cancer Genome Atlas(TCGA) to conduct gene expression differences and survival analysis of the key genes. Results Totally 218 differential genes were screened out. KEGG pathway analysis showed that the differential genes were mainly enriched in salivary secretion, ECM receptor interaction, cell cycle and other pathways. The key genes of CHEK1, SERPINE1, SPP1, COL1 A1, FOXM1, MMP9, CXCL12 and MMP1 were screened out by using cystoscape software. The key genes were input into GEPIA database to search for similar genes, and all genes were input into Metascape for enrichment analysis, mainly concentrated in extracellular tissue structure, PID integrin 1 pathway, mitotic chromosome separation, etc. The differences of expression of key genes in laryngeal cancer tissues and normal tissues were analyzed using TCGA database data, and all key genes had statistical significance. In the survival analysis, we found that the expressions of COL1 A1 and MMP1 were significantly correlated with the overall survival rate of laryngeal cancer. Conclusion The differential genes and key genes found in this study can help us to understand the molecular mechanism of laryngeal cancer and provide a new candidate target for the diagnosis and treatment of laryngeal cancer.更多还原