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目的利用生物信息学模块化分析方法,筛选头颈部鳞癌中的功能性基因模块,为头颈部鳞癌的研究和治疗提供新的靶点。方法获取GEO数据库中头颈部鳞癌的全基因组数据(GSE6631)后,利用R语言limma包筛选头颈部鳞癌中差异表达基因。通过STRING数据库,建立头颈部鳞癌中差异表达基因的蛋白-蛋白互作网络。然后,利用Cytoscape软件的MCODE插件筛选头颈部鳞癌中的基因模块。利用DAVID数据库,获得模块功能。最后,挖掘模块基因中的蛋白激酶基因并利用Selleckchem数据库筛选其激酶抑制剂。结果共筛选出头颈部鳞癌中的差异表达基因929个(P<0.05且|Fold Change|≥2)。根据String数据库,发现这些差异基因中共有5 588个蛋白质互作对,并据此建立鼻咽癌中的蛋白质互作网络。利用MCODE方法在蛋白质互作网络中共筛选出3个基因模块。GO分析显示这些模块与头颈部鳞癌的关系十分密切,主要包括参与细胞周期、细胞增殖、细胞黏附、细胞凋亡等重要肿瘤细胞活动。3个模块包含3个蛋白激酶基因,即CDK1、CDK4和CDK5,共筛选出调控它们的39个激酶抑制剂,其中20个对头颈部鳞癌的作用还不清楚,具有成为抗癌新药的潜力。结论头颈部鳞癌中的3个功能性基因模块可能在头颈部鳞癌的发生发展中发挥重要作用,20个激酶抑制剂可能通过调控CDK家族基因来调控头颈部鳞癌的发生发展,这些功能性模块的挖掘和激酶抑制剂的筛选可能为头颈部鳞癌的研究和治疗提供新的靶点。
Objective To use modular analysis of bioinformatics to screen functional gene modules in head and neck squamous cell carcinoma and provide new targets for the study and treatment of head and neck squamous cell carcinoma. METHODS: Genome data of head and neck squamous cell carcinoma (GSE6631) in the GEO database were obtained, and differentially expressed genes in head and neck squamous cell carcinoma were screened using the R language limma package. A protein-protein interaction network for differentially expressed genes in head and neck squamous cell carcinoma was established using the STRING database. Then, use the MCODE plug-in from Cytoscape software to screen the gene modules in head and neck squamous cell carcinoma. Use the DAVID database to get module functionality. Finally, the protein kinase genes in the module genes were mined and their kinase inhibitors screened using the Selleckchem database. Results A total of 929 differentially expressed genes were identified in head and neck squamous cell carcinoma (P<0.05 and |Fold Change|≥2). According to the String database, a total of 5,588 protein interaction pairs were found among these differential genes, and a protein interaction network in nasopharyngeal carcinoma was established accordingly. Three gene modules were screened in the protein interaction network using the MCODE method. GO analysis showed that these modules are closely related to head and neck squamous cell carcinoma, mainly involved in cell cycle, cell proliferation, cell adhesion, apoptosis and other important tumor cell activity. Three modules contained three protein kinase genes, namely CDK1, CDK4, and CDK5. A total of 39 kinase inhibitors were screened to regulate them. Of these, 20 were not known for the role of head and neck squamous cell carcinoma, and they have the potential to become new anticancer drugs. . Conclusion Three functional gene modules in head and neck squamous cell carcinoma may play an important role in the development of head and neck squamous cell carcinoma. Twenty kinase inhibitors may regulate the occurrence and development of head and neck squamous cell carcinoma by regulating CDK family genes. The exploration of these functional modules and the screening of kinase inhibitors may provide new targets for the study and treatment of head and neck squamous cell carcinoma.