卵巢癌预后不良基因ATP6V1F、GINS1、GINS4的筛选  

Screening of the Poor Prognosis Genes ATP6V1F,GINS1 and GINS4 in Ovarian Cancer

作　　者：饶玉梅[1] 王欣欣[1] RAO Yumei;WAN Xinxin(Department of Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院妇科,河南郑州450052

出　　处：《河南医学研究》2023年第9期1586-1593,共8页Henan Medical Research

基　　金：国家自然科学基金资助项目(82201787);河南省高等学校重点科研项目(18A310031)。

摘　　要：目的 筛选卵巢癌预后不良的分子生物学标志。方法 从GEO数据库获得卵巢癌GSE14001、GSE14407数据集,用在线分析工具GEO2R、Venn筛选得到卵巢癌和正常卵巢组织差异表达基因(DEGs),对DEGs进行富集分析,构建蛋白互作网络(PPI),以及构建网络模块得到关键基因,利用Kaplan Meier plotter网站分析关键基因与卵巢癌患者总生存期之间关系,应用GEPIA数据库分析DEGs在卵巢和卵巢癌组织中表达,应用The Human Protein Atlas数据库获取筛选基因的免疫组化结果,对比它们在卵巢和卵巢癌组织间的表达差异。结果 得到211个DEGs,92个上调和119个下调。差异基因生物学过程主要涉及侧枝发芽的正向调控、乏氧反应、间充质-上皮细胞信号传导;细胞组分主要集中在质膜顶、细胞表面、细胞外外泌体等部位;分子功能主要涉及丝氨酸型内肽酶活性、金属内肽酶活性、受体活性等;信号通路富集于白细胞跨内皮细胞迁移、细胞黏附通路、癌症通路等信号通路。得到35个候选基因,其中14个基因高表达、8个基因低表达与患者总生存期相关(P<0.05)。其中ATP6V1F、GINS1、GINS4基因在卵巢癌组织中在RNA水平和蛋白质水平表达均高于正常组织(P<0.05)。GNB3在卵巢癌组织中RNA水平表达低于正常组织,而在蛋白质水平恰好相反(P<0.05)。结论 ATP6V1F、GINS1、GINS4有可能是卵巢癌预后不良的新分子标志物。Objective To screen the molecular biological markers of poor prognosis in ovarian cancer.Methods Ovarian cancer GSE14001 and GSE14407 datasets were obtained from the GEO database,differentially expressed genes(DEGs)were selected using tools of GEO2R and Venn.Protein interaction(PPI)network was constructed by string database for these DEGs,MCODE plug-in was constructed to obtain key genes.Kaplan Meier plotter was used to analyze the relationship between key genes and the overall survival of ovarian cancer patients.GEPIA database was utilized to analyze DEGs expression in ovarian and ovarian cancer tissues.The Human Protein Atlas database was applied to obtain the immunohistochemistry results of the screened genes to contrast their expression differences between normal ovarian and ovarian cancer tissues.Results There were 211 DEGs,including 92 up-regulated and 119 down-regulated genes.The biological process of DEGs mainly involved positive regulation of collateral sprouting,response to hypoxia,mesenchymal-epithelial cell signaling etc.The cell components were mainly concentrated in plasma membrane top,cell surface,extracellular exosome and other parts,and the molecular functions mainly involved serine-type endopeptidase activity,metal endopeptidase activity,receptor activity and glutathione binding.The signaling pathway was enriched in leukocyte transendothelial migration,cell adhesion molecules,pathways in cancer,and proteoglycans in caner.A totaly of 35 candidate genes were obtained from DEGs,of which 14 high expression and 8 low expression genes were associated with patient overall survival(P<0.05).Among them,ATP6V1F,GINS1 and GINS4 genes were more expressed in RNA and protein levels in ovarian cancer than in normal tissues.However,GNB3 was expressed at lower RNA levels in ovarian cancer than in normal tissues,while the opposite was observed at protein levels.Conclusion ATP6V1F,GINS1 and GINS4 may be new molecular markers of poor prognosis in ovarian cancer.

关 键 词：卵巢癌 ATP6V1F GINS1 GINS4 生物信息学 

分 类 号：R737.31[医药卫生—肿瘤]