基因集富集分析探讨HER2基因对胃癌代谢的影响  

Study on the impact of HER2 expression on the metabolism of gastric cancer with gene set enrichment analysis

作　　者：刘虎[1] 吴思浛 包楚阳 李文娟[1] 周守兵 金伟[1] Liu Hu;Wu Sihan;Bao ChuYang(Dept of Oncology,West District of Affiliated Hospital of University of Science and Technology of China,Anhui Provincial Cancer Hospital,Hefei 230031;Dept of Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]中国科学技术大学附属第一医院西区,安徽省肿瘤医院肿瘤化疗科,合肥230031 [2]安徽医科大学第一附属医院肿瘤内科,合肥230022

出　　处：《安徽医科大学学报》2020年第9期1339-1342,1349,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81472750)。

摘　　要：目的运用基因集富集分析(GSEA)探索人表皮生长因子受体2(HER2)基因表达状态对胃癌代谢通路影响情况。方法下载癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和欧洲生物信息研究所(ArrayExpress)数据库的胃癌转录表达数据库,根据Her2拷贝数或者表达水平选取高低表达组,应用GSEA软件进行富集分析,取错误发现率q值(FDR q val)<25%和/或名义P值(nom P val)<0.01的代谢通路作为有意义的代谢基因集,结果绘制热图寻找共性。结果在癌症基因组图谱胃腺癌集(TCGA STAD)、GEO数据集(GSE66229)等10个数据库中,Her2的高低表达对对过氧物酶体、N-聚糖生物合成和嘧啶代谢通路基因集有影响(FDR q val<25%且nom P val<0.01),糖基磷脂酰肌醇、甘油磷脂、鞘脂类代谢差异有统计学意义(nom P val<0.01)。结论多个数据库GSEA分析结果提示癌基因Her2的状态与多个代谢通路基因集有相关性。Objective To explore the impact of the status of human epidermal growth factor receptor 2 gene(HER2)gene on the metabolism of gastric cancer with computational gene sets enrichment analysis(GSEA).Methods The expression datasets of gastric cancer were downloaded from the cancer genome atlas(TCGA),gene expression omnibus(GEO)and ArrayExpress.Phenotype labels of Her2 high and low expression were made,which were applied in the GSEA.The meaningful metabolic genesets were found at false discovery rate(FDR)q value<25%and/or nominal P value<0.01.Heatmap was made to compare the meaningful gene sets in different data-sets.Results Among the 10 datasets including TCGA STAD and GSE66229,peroxisome,N-glycan and pyrimidine metabolisms were significantly affected at FDR q val<25%and nom P val<0.01,glycosylphospatidylinositol GPI anchor biosynthesis,glycerolphosphalipid metabolism and sphingolipid metabolism at P value<0.01.Conclusion Multiple metabolic gene sets are affected by Her2 status with evidences in multiple datasets.

关 键 词：胃癌 癌症基因组图谱 基因集富集分析 人类表皮生长因子受体2 京都基因与基因组百科全书 代谢 

分 类 号：R735.2[医药卫生—肿瘤]