喉癌中差异表达的蛋白激酶及其抑制剂的生物信息学筛选.

Objective: Screening differentially expressed protein kinases and their inhibitors to provide new targets for molecular therapy of laryngeal. Methods: Pubmed database and SAM software were employed to screen the differentially expressed protein kinase gene in larybgeal cancer. Hep-2 and Fa Du cells were cultured in vitro. Real-time PCR was used to prove the accuracy of microarray results. Based on KEGG database, these kinase regulated pathways were identified. The kinase inhibitors of differentially expression were identified by literature mining and artificial screening. Results: ① 207 differentially expressed genes including 4 protein kinases(CDC42, CDK7, SLK, TXK) were identified in whole genome profiling(P<0.05). ② The results of Real-time PCR showed that 4 kinase genes were differentially expressed in Hep-2 and Fa Du cells, which consistent with the microarray results(P<0.05). ③ The results of pathway analysis showed 25 pathways were regulated by the 4 kinases. ④ The results of literature mining and artificial screening showed that 10 inhibitors regulated CDC42; 7 inhibitors regulated CDK7; 1 inhibitor regulated SLK and 2 inhibitors regulared TXK. Among them, 9 inhibitors have few studies in cancer terms(n<10). Conclusion: 4 differentially expressed protein kinases(CDC42, CDK7, SLK, TXK) were identified. Their kinase inhibitors may potential have a role in anti-cancer, which provided a new target point for molecular therapy of laryngeal cancer. [ABSTRACT FROM AUTHOR]

目的:筛选喉癌中差异表达的激酶基因以及调控这些差异表达激酶的激酶抑制剂,为喉癌的分子治疗提供新的靶点.方法:利用PubMed数据库和SAM软件筛选喉癌中差异表达的激酶基因.体外培养人喉癌Hep-2和FaDu细胞.实时定量聚合酶链反应(Real-time PCR)检测目的激酶在喉癌细胞系中的表达,以验证全基因表达谱结果的准确性.利用KEGG数据库获得激酶调控的通路.文献挖掘和人工筛选获得差异表达激酶的激酶抑制剂.结果:①在喉癌基因组表达谱中,共筛选出差异表达基因207个,P＜0.05,其中激酶基因4个,分别为CDC42、CDK7、SLK和TXK.②Real-time PCR结果显示在人喉癌Hep-2和FaDu细胞中这四个差异基因也出现差异表达,P＜0.05,证明全基因组的结果准确.③通路分析的结果显示4个差异激酶共调控25个通路.④文献挖掘和人工筛选的结果显示共有10个激酶抑制剂调控CDC42,7个激酶抑制剂调控CDK7,1个激酶抑制剂调控SLK,2个激酶抑制剂调控TXK.并且再次文献挖掘的结果显示在这20个激酶抑制剂中,有9个在癌症方面的研究较少,文献＜10篇.结论:喉癌中共有四个激酶CDC42、CDK7、SLK和TXK发生差异表达,并发挥促癌作用.它们的激酶抑制剂可能有潜在的抗癌作用,为喉癌的分子治疗提供新的切入点. [ABSTRACT FROM AUTHOR]