摘要/Abstract
摘要： 目的·探究食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）的发生机制及其潜在靶向药物，为诊断和治疗ESCC提供理论依据。方法·选取2个GEO集（GSE38129、GSE20347），用R语言筛选差异表达基因（differentially expressed genes，DEGs）并进行GO（Gene Ontology）和KEGG（Kyoto Encyclopedia of Genes and Genomes）富集分析。对DEGs行蛋白质相互作用（protein-protein interaction，PPI）网络分析，获得最显著模块基因以及关键基因，并对关键基因磷酸化酶B激酶（phosphorylase B kinase，PBK）做靶向药物预测。结果·2个数据集共包含670条相同的DEGs，其中下调基因342条、上调基因328条。GO和KEGG富集分析结果显示，DEGs主要富集到细胞外结构的组织、细胞外基质的组织、p53信号通路、IL-17信号通路、细胞周期等通路。通过对PPI网络做密集度分析，共筛选出20条关键基因。其中，关键基因PBK与细胞周期相关，在2个数据集中表达量均有上调；通过变构位点探测和化合物库虚拟筛选，预测出了PBK的潜在药物Compound 1。结论·通过生物信息学的方法能够有效分析ESCC的关键基因。关键基因PBK的靶向药物预测结果可能为ESCC的靶向治疗提供一定的参考。
关键词: 食管鳞状细胞癌, 差异表达基因, GO富集分析, KEGG富集分析, 蛋白质相互作用网络, 靶向药物预测
Abstract:
Objective · To explore the mechanism of esophageal squamous cell carcinoma (ESCC) and its potential targeted drugs, and to provide the theoretical basis for diagnosis and treatment of ESCC. Methods · Two GEO sets GSE38129 and GSE20347 were selected, and differentially expressed genes (DEGs) were screenedR language. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were conducted for DEGs. The most significant module genes and key genes were analyzedprotein-protein interaction (PPI) network for DEGs. Targeted drug prediction was made for phosphorylase B kinase (PBK). Results · A total of 670 DEGs were identified, consisting of 342 down-regulated genes and 328 up-regulated genes. The enriched functions and pathways of DEGs included extracellular structure organization, extracellular matrix organization, p53 signaling pathway, IL-17 signaling pathway and cell cycle. Twenty key genes were identifiedanalyzing DEGs’ PPI network. The key gene PBK was related to the cell cycle, and the of PBK was up-regulated in the two data sets. The potential drug Compound 1 of PBK was predictedallosteric site detection and compound library virtual screening. Conclusion · The key genes of ESCC can be effectively analyzedbioinformatics. The prediction results of targeted drugs of key gene PBK may provide reference for the targeted therapy of ESCC.
Key words: esophageal squamous cell carcinoma (ESCC), differentially expressed gene (DEG), GO enrichment analysis, KEGG enrichment analysis, protein-protein interaction (PPI) network, targeted drug prediction
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