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作 者:刘艳娇[1] 关凤英[1] 李小坤[1] 谭诚 陈丽梅 王玉祥[2] Liu Yanjiao;Guan Fengying;Li Xiaokun;Tan Cheng;Chen Limei;Wang Yuxiang(Handan First Hospital, 056000;Hebei Medical University Fourth Hospital, Shijiazhuang, 050000)
机构地区:[1]邯郸市第一医院,邯郸056000 [2]河北医科大学第四医院,石家庄050000
出 处:《基因组学与应用生物学》2018年第7期3164-3176,共13页Genomics and Applied Biology
基 金:邯郸市第一医院提供资助
摘 要:分析食管基底细胞样鳞癌(basaloid squamous cell carcinoma of the esophagus,BSCCE)的组织样本基因表达情况,探讨其病理学过程和肿瘤免疫逃逸机制,同时对BSCCE独特的肿瘤微环境及潜在的临床指标在对其远期预后的病理基础进行讨论,以期为临床工作中更好的治疗BSCCE提供一定的理论基础。利用临床术中获取的组织样本及其基因芯片数据,进一步获取BSCCE组织样本与同体正常组织样本的基因差异表达情况(log|FC|≥2,p〈0.05),其中BSCCE组织相对于正常组织的上调表达差异表达基因共489个,下调差异表达基因922个,利用DAVID在线分析系统对差异表达基因进行京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路分析获取对BSCCE组织病理情况相关的分析结果,进一步利用STRING-OL工具对差异表达基因的可信度(可信度≥0.4)进行筛选,获取差异表达基因的蛋白质相互作用分析(protein-protein interaction,PPI)结果,进一步利用Cytoscape软件对筛选后的PPI结果制作相应的基因相互作用网状图,并进一步筛选核心表达的差异基因。在上调差异基因的KEGG分析中获得了88个结果,如p53signaling pathway、Cytokine-cytokine receptor interaction pathway、Toll-like receptor signaling pathway等,在下调的差异基因KEGG分析中获得了125个结果,如Drug metabolism-cytochrome P450 pathway、MAPK signaling pathway、Calcium signaling pathway、Cytokine-cytokine receptor interaction pathway等,这些相关的信号通路对进一步理解BSCCE的肿瘤微环境变化及肿瘤病理相关机制有重要意义,通过PPI分析,我们筛选出了一些与肿瘤远期生存率(overall survival,OS)相关的基因:CDC6、CDC20、TOP2A、NEK2、CDC25A等,这为我们进一步研究BSCCE及其肿瘤病理标志物和远期生存的关系提供了理论基础。To further understand the basaloid squamous cell carcinoma of the esophagus, BSCCE, with the pathological characteristic of BSCCE and excavate potential therapeutic targets, so as to improve the Overall survival for the clinical treatment. This study using bioinformatics methods and the technology of gene chip, The tissue samples of BSCCE were analyzed. The expression gene (489 up-regulated and 922 down-regulated, log|FC|≥2, p 〈0.05) which related to the possible process of pathology and tumor immune escape mechanism will be discuss and assay by kyoto encyclopedia of genes and genomes (KEGG) and protein-protein interaction (PPI). In the assay, DAVID and STRING-OL (credibility≥ 0.4) was be used. Then the Cytoscape software was used to constrtict protein-protein interaction network, with the up-regulated expression genes, the KEGG study shows 88 results, such as 53 signaling pathway, cytokine-cytokine receptor interaction pathway, toll-like receptor signaling pathway and et al, In the down-regulated expression genes, the KEGG study shows 125 results, such as Drug metabolism-cytochrome P450 pathway, MAPK signaling pathway, calcium signaling pathway, cytokine-cytokine receptor interaction pathway. All of these signaling pathway have the correlation with tumor microenvironment. At the same time, the Overall survival and tumor micro- environment of BSCCE has be discussion by PPI assay, such as CDC6, CDC20, TOP2A, NEK2, CDC25 and et al.. This research is a base for more BSCCE or SCC clinical study and treatment.
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