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目的筛选下咽癌中差异表达的激酶基因及其选择性抑制剂,为下咽癌的分子靶向治疗提供新的参考。方法利用GEO数据库和SAM软件筛选下咽癌中差异表达的激酶基因,体外培养人下咽癌Fa Du细胞系。为验证GEO数据库中芯片结果的准确性,利用实时定量聚合酶链反应(Real-time PCR)检测差异表达激酶在Fa Du细胞中的表达量,通过KEGG数据库获得激酶调控的通路,利用激酶抑制剂数据库和文献挖掘筛选获得在下咽癌Fa Du细胞系中差异表达激酶的选择性抑制剂。结果 1在GEO数据库的下咽癌基因组表达谱中,共筛选出3个高表达的激酶基因,分别为PKC-β、CDK6和CDC42(差异倍数≥2.0且P<0.05);2Real-time PCR结果显示在人下咽癌Fa Du细胞中这3个上调激酶基因也出现高表达(P<0.05),证明全基因组的结果准确;3KEGG通路分析的结果显示3个高表达激酶调控复杂的通路网络;4激酶抑制剂的筛选结果显示共有5个激酶抑制剂调控PKC-β,4个激酶抑制剂调控CDK6,3个激酶抑制剂调控CDC42。文献挖掘的结果显示在这12个激酶抑制剂中,有4个在癌症方面的研究较少,文献<10篇。结论下咽癌中共有3个激酶PKC-β、CDK6和CDC42发生高表达,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,为下咽癌的分子治疗提供新的切入点。
Objective To screen differentially expressed kinase genes and their selective inhibitors in hypopharyngeal carcinoma and provide a new reference for molecular targeted therapy of hypopharyngeal carcinoma. Methods The gene of kinases differentially expressed in hypopharyngeal carcinoma was screened by GEO database and SAM software, and Fa Du cell lines were cultured in vitro. In order to verify the accuracy of microarray results in GEO database, the expression of differentially expressed kinases in Fa Du cells was detected by Real-time PCR. The kinase-regulated pathway was obtained by KEGG database. Database and literature mining screening obtained in the Du Du Xia Fa Fa cell lines differentially expressed kinase selective inhibitors. Results1 Three highly expressed kinase genes were screened in the GEO database for hypopharyngeal cancer genomes, which were PKC-β, CDK6 and CDC42 respectively (difference multiple 2.0 and P <0.05). The result of 2 Real-time PCR The results of 3KEGG pathway analysis showed that three high-expression kinases regulate the complex pathway network. The results of 3KEGG pathway analysis showed that the three high-expression kinases regulate the complex pathway network. 4 kinase inhibitor screening results showed that a total of 5 kinase inhibitors regulate PKC-β, 4 kinase inhibitors regulate CDK6, 3 kinase inhibitors regulate CDC42. The results of literature mining showed that of the 12 kinase inhibitors, four had less research on cancer, and the literature <10 articles. Conclusions There are three kinases PKC-β, CDK6 and CDC42 in hypopharyngeal carcinoma which are highly expressed and play a role of promoting cancer. Their kinase inhibitors may have potential anti-cancer effects, providing a new entry point for the molecular treatment of hypopharyngeal cancer.