宫颈癌中高表达蛋白激酶及其抑制剂的生物信息学筛选

Bioinformatic Screening of Highly Expressed Protein Kinases and Their Inhibitors in Cervical Cancer

本研究运用生物信息学方法筛选宫颈癌中高表达的蛋白激酶及其抑制剂,为宫颈癌的分子靶向治疗提供参考。从基因表达数据库(Gene Expression Omnibus, GEO)下载宫颈癌表达谱芯片数据GSE63514,筛选高表达激酶基因;使用clusterProfiler软件包进行GO富集分析和KEGG通路分析;从激酶-激酶抑制剂相互作用图谱中筛选高表达激酶对应的最具选择性的抑制剂,并通过文献挖掘技术进行评估。筛选得到差异表达基因1 167个,其中高表达激酶基因33个。GO分析结果显示,高表达激酶基因主要富集在蛋白磷酸化、细胞周期和DNA损伤等生物学过程。KEGG通路分析表明,这些激酶基因主要富集在细胞周期、p53信号通路、卵母细胞减数分裂和人乳头状瘤病毒(human papilloma virus, HPV)感染等通路。通过激酶-激酶抑制剂相互作用图谱,得到最具潜力的8个高表达激酶,对应最具选择性激酶抑制剂16个。文献挖掘的结果显示这16个激酶抑制剂在肿瘤中均有研究,但有8种抑制剂与宫颈癌没有关联文献,具有成为抗宫颈癌新药物的潜力,可为宫颈癌的靶向治疗提供新的参考。

This study used bioinformatics methods to screen highly expressed protein kinases and their inhibitors, which may provide references for molecular targeted therapy in cervical cancer. Expression profile dataset GSE63514 was downloaded from GEO database, and the highly expressed protein kinase genes were identified. GO enrichment and KEGG pathway analysis were conducted with clusterProfiler package. The most selectivity inhibitors of highly expressed kinases were selected based on kinase-kinase inhibitor interaction map and eva-luated them with literature mining. A total of 1 167 differentially expressed genes were identified from the expression profile dataset, of which 33 were highly expressed kinase genes. GO analysis showed that these genes were mainly enriched in protein phosphorylation, cell cycle, DNA damage and other biological processes. KEGG pathway analysis indicated that these genes were enriched in cell cycle, p53 signaling pathway, oocyte meiosis and human papilloma virus(HPV) infection pathways. Based on the kinase-kinase inhibitor interaction map, the most potent 8 highly expressed kinases correspond to 16 most selective kinase inhibitors were identified. The results of the literature mining showed that the 16 inhibitors have been studied in tumors, but 8 of them have no literature associations with cervical cancer and have potential to become new drugs against cervical cancer, which might provide new references for cervical cancer targeted therapy.