鼻咽癌中高表达蛋白激酶及其抑制剂的生物信息学筛选

摘要

目的：筛选鼻咽癌中高表达的激酶基因以及调控这些激酶的激酶抑制剂，为鼻咽癌的分子治疗提供新的切入点。方法利用 GEO 数据库和 SAM软件筛选鼻咽癌中高表达的激酶基因；利用 DAVID 数据库获得激酶调控的生物学功能；利用 Sell-eckchem 数据库筛选调控这些高表达激酶的激酶抑制剂，再通过文献挖掘技术筛选潜在的抗鼻咽癌新药。结果在鼻咽癌基因组中，我们共筛选出差异表达基因2360个，其中高表达激酶基因21个，分别为 CHEK1、CHEK2、PRKDC、AURKA、VRK2、STK17A、MELK、NUAK1、TRPM7、MASTL、AXL、BUB1、BUB1B、CDK4、TTK、CDC7、CASK、AKT3、TBK1和 PBK（Fold Change≥2且 P ＜0．05）。功能分析的结果显示21个高表达激酶主要参与10个功能 term 中，包括调节细胞活动相关功能，如“protein amino acid phosphoryla-tion”“phosphorylation”“phosphate metabolic process”和调控细胞周期相关功能，如“mitotic cell cycle”“cell cycle phase”“regulation of cell cycle”等。通过 Selleckchem 数据库，我们发现9个高表达激酶具有已被证实的激酶抑制剂51个。文献挖掘的结果显示在这51个激酶抑制剂中，有18个在癌症方面的研究较少，文献小于10篇，具有成为抗鼻咽癌潜力的新药物。结论鼻咽癌中共有21个激酶高表达，并可能通过调控肿瘤细胞周期等生物学功能来发挥促鼻咽癌作用；它们的抑制剂可能有潜在的抗癌作用，为鼻咽癌的分子治疗提供新的靶点。%Objective To screening up-regulated protein kinases and their inhibitors in order to provide new targets for molecular thera-py of nasopharyngeal cancer.Methods GEO database and SAM software were employed to screen the up-regulated protein kinase gene in nasopharyngeal cancer.Based on DAVID database,the regulating functions of kinases were identified.The inhibitors of up-regulated kinase genes were identified by Selleckchem database.Literature mining was used to screen the potential anti-cancer drugs.Results Totally 2360 differentially expressed genes including 21 up-regulated protein kinases (CHEK1,CHEK2,PRKDC,AURKA,VRK2,STK17A,MELK,NU-AK1,TRPM7,MASTL,AXL,BUB1,BUB1B,CDK4,TTK,CDC7,CASK,AKT3,TBK1 and PBK)were identified in the whole genome profi-ling (Fold Change≥2,P <0.05).The results of function analysis showed the up-regulated genes were enriched in 10 function terms such as‘protein amino acid phosphorylation’‘phosphorylation’‘phosphate metabolic process’‘mitotic cell cycle’‘cell cycle phase’‘regulation of cell cycle’,and so on.The Selleckchem database analysis showed there were 9 up-regulated protein kinases equipped with 51 inhibitors which were proved already.The results of literature mining showed that 18 inhibitors of them had a few studies (less than 10 literatures)in cancer terms,and there was a potential to become new drugs to treat nasopharyngeal cancer.Conclusion A total of 21 up-regulated protein kinases were identified,and they might promote the nasopharyngeal carcinoma by regulating functions such as the cell-cycle control pathway.Their ki-nase inhibitors may have a potential role in anti-cancer treatment,which provided a new target point for molecular therapy of nasopharyngeal cancer.