胃癌顺铂抵抗相关免疫标记基因的富集分析  

The enrichment analysis of immunologic signature genes associated with cisplatin resistance in gastric cancer

作　　者：汪圣毅[1] 程彦 李旭升 闫亚飞[1] 张尚鑫[1] 闫强[1] 李永翔[1] Wang Shengyi;Cheng Yan;Li Xusheng(Dept of Gastrointestinal Surgery, Dept of General Surgery, The FirstAffiliated Hospital of Anhui Medical University, Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院普外科胃肠外科,合肥230022

出　　处：《安徽医科大学学报》2020年第2期200-204,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81874063)。

摘　　要：目的采用基因集富集分析(GSEA)方法寻找胃癌抵抗顺铂的免疫标记基因(ISGs)。方法用GEO数据库的GSE94714数据集,GEO2R分析差异基因,观察条件筛选对基因数的作用,GSEA纳入耐药、未耐药组胃癌细胞的全部差异表达基因,与分子标签数据库比较,获取ISGs,交集筛选,Kaplan Meier Plotter分析交集基因对胃癌预后的影响。结果差异表达基因共34183个,其中上调12452个、下调17381个,筛选差异倍数的增加使排除基因数增加。GSEA富集到标准化富集评分(NES)排序前6的条目(P<0.01),其中的交集基因包括线粒体核糖体蛋白L12、富含脯氨酸蛋白13、毛状蛋白样F-肌动蛋白结合蛋白1、聚(RC)结合蛋白1、艾杜糖2-硫酸酯酶、LIM结构域2、富含嘌呤元素结合蛋白A、小视觉叶同源物、CCR 4-非转录复合物亚单位3、转化生长因子β1、二酰甘油激酶ζ、接头蛋白2,12个基因与胃癌的总生存时间有关,均具有统计学意义(P<0.05)。结论GSEA方法可有效获取胃癌顺铂抵抗的ISGs,新发现的基因作为潜在靶点,可促进胃癌化疗抵抗机制的研究。Objective To explore the immunologic signature genes(ISGs)associated with cisplatin resistance in gastric cancer based on gene set enrichment analysis(GSEA).Methods GSE94714 dataset from GEO database was used,and the differentially expressed genes(DEGs)were analyzed with GEO2R.The effects of conditional gene screening on gene number were observed.GSEA included all DEGs from gastric cancer cells in drug resistant and non-resistant groups.The DEGs were compared with the molecular signatures database(MSigDB),and the obtained ISGs were screened for intersection,and the effects of ISGs on the prognosis of gastric cancer were analyzed by Kaplan Meier Plotter method.Results A total of 34183 DEGs included 12452 up-regulated and 17381 down-regulated genes.The increased fold change(FC)added the number of excluded genes.Six entries with the top normalized enrichment score(NES)were identified by GSEA(P<0.01).The intersection ISGs included mitochondrial ribosomal protein L 12(MRPL12),proline-rich protein 13(PRR13),coactosin like F-actin binding protein 1(COTL1),poly(RC)binding protein 1(PCBP1),iduronate 2-sulfatase(IDS),LIM domain containing 2(LIMD2),purine rich element binding protein A(PURA),small optic lobes homolog(SOLH),CCR4-NOT transcription complex subunit 3(CNOT3),transforming growth factor beta 1(TGFβ1),diacylglycerol kinase zeta(DGKZ),and docking protein 2(DOK2).Twelve ISGs were associated with the overall survival time of gastric cancer,all of which were statistically significant(P<0.05).Conclusion The GSEA method can effectively extract the ISGs of cisplatin resistance in gastric cancer.Newly discovered ISGs,as potential targets,can enhance the study of chemoresistant mechanisms in gastric cancer.

关 键 词：胃癌 化疗抵抗 基因集富集分析 基因表达数据库 免疫标记基因 预后 

分 类 号：R735.2[医药卫生—肿瘤]