摘要
目的鉴定胃腺癌新的预后标志物和治疗靶点。方法通过Gene Expression Omnibus(GEO)数据库下载GSE33335和GSE63089基因表达数据集,共含有70例胃腺癌组织和配对的胃正常组织基因芯片数据,使用R语言分析胃癌组织和胃正常组织间差异表达基因。通过String在线分析工具构建差异表达基因的蛋白-蛋白相互作用(PPI)网络。使用Cytoscape软件和分子复合物检测(MCODE)插件分离出关键基因集。使用在线数据库鉴定分离出与预后相关的关键基因,分别用数据库信息和南通大学附属医院2019年7—9月收治的32例胃腺癌组织和癌旁正常组织从mRNA和蛋白水平进行验证。结果使用R语言分析显示,2个数据集中有128个共同差异表达基因,其中85个基因在胃腺癌组织中表达上调,43个基因在胃腺癌组织中表达下调。通过String在线工具和Cytoscape软件建立了PPI网络和MCODE模型,获得27个关键基因,其中有25个基因与胃腺癌患者的预后有关(P<0.05)。25个与预后相关的基因中,有14个基因在胃腺癌组织中表达显著,其中有3个基因[垂体瘤转化基因1(PTTG1)、细胞周期蛋白B1(CCNB1)和polo样激酶1(PLK1)]在细胞周期途径中显著富集。PTTG1在胃腺癌和胃正常组织中的阳性表达率分别为68.8%(22/32)和18.8%(6/32),差异有统计学意义(P<0.05)。结论 PTTG1在胃腺癌组织和胃正常组织中存在表达差异,是胃腺癌形成的关键基因。过表达PTTG1的胃腺癌患者预后更差。PTTG1可能通过调控细胞周期参与胃腺癌的发生发展。
Objective To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma.Methods The public datasets of gastric adenocarcinoma collected from GEO database(GSE33335 and GSE63089)were downloaded for analysis.There were 70 GC tissues and paired normal tissues in the two profile datasets.Differentially expressed genes(DEGs)between GC tissues and normal stomach tissues were selected by the R software.Protein-protein interaction(PPI)of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes(STRING).The key gene sets were analyzed by Cytoscape and Molecular Complex Detection(MCODE).The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University.Results DEGs were identified in the two datasets by using R software.A total of 128 DEGs were detected,including 85 up-regulated genes(log_(2)FC>1.2 and FDR<0.01)and 43 down-regulated genes(log_(2)FC<-1.2 and FDR<0.01)in the GC tissues.PPI network model and MCODE model were established by using the Online String tool and Cytoscape software,and 27 key genes were obtained,including 25 genes related with prognosis of GC patients(P<0.05).We identified 14 significant DEGs in GC tissues,including cyclin B1(CCNB1),polo-like kinase 1(PLK1)and pituitary-tumor transforming gene(PTTG1),which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis.The positive expression rate of PTTG1 in GC tissues was 68.8%(22/32),significantly higher than 18.8%(6/32)in normal gastric tissues(P<0.05).Conclusions The expression of PTTG1 is different in GC and gastric tissues,implicates it is the key gene in gastric carcinogenesis.The prognoses of GC patients with higher PTTG1 expression are worse.PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.
作者
姚宁华
陈志明
石宇
严晓娣
吕丽婷
刘静
宣婷婷
钱静
赵洪瑜
Yao Ninghua;Chen Zhiming;Shi Yu;Yan Xiaodi;Lyu Liting;Liu Jing;Xuan Tingting;Qian Jing;Zhao Hongyu(Department of Radiation Oncology,Affiliated Hospital of Nantong University,Nantong 226001,China;Department of Chemotherapy,Affiliated Hospital of Nantong University,Nantong 226001,China;Department of Radiation Oncology,Nantong First People's Hospital,Nantong 226001,China)
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2021年第3期306-311,共6页
Chinese Journal of Oncology
基金
国家青年基金(81602010)。
