基于多组学数据分析复制因子C4在肝细胞癌中的表达及预后  

Expression of RFC4 and its prognostic role in hepatocellular carcinoma:An analysis based on multi-omics data

作　　者：邓剑雄 邱峰[1] 钟方炎 顾伟国 余锋[1] DENG Jianxiong;QIU Feng;ZHONG Fangyan;GU Weiguo;YU Feng(Department of Oncology, the First Affiliated Hospital of Nanchang University, Nanchang 330000, China)

机构地区：[1]南昌大学第一附属医院肿瘤科,南昌330000

出　　处：《临床肿瘤学杂志》2020年第8期717-723,共7页Chinese Clinical Oncology

摘　　要：目的探讨复制因子C4(RFC4)作为肝细胞癌(HCC)潜在的预后标志物及其临床意义。方法使用基因表达谱分析(GEPIA)、Oncomine、UALCAN、人类蛋白图谱数据库和Kaplan-Meier plotter网站,分析RFC4 mRNA和蛋白在HCC中的表达,探讨其表达水平与HCC临床病理特征和预后的关系。通过cBioPortal网站分析HCC中RFC4的基因突变、拷贝数变异、mRNA表达及与预后的关系。利用String、Metascape数据库和Cytoscape软件对共表达基因和蛋白间的相互作用进行分析及可视化处理,并预测其生物学功能。结果与正常组织相比,RFC4 mRNA在HCC中显著高表达(P=4.58×10-8),同时发现RFC4 mRNA的表达水平与HCC的淋巴结转移、肿瘤分期及病理分级有关(P<0.05)。生存分析结果显示,相比RFC4 mRNA低表达组,RFC4 mRNA高表达组患者的总生存时间(HR=1.81,95%CI:1.26~2.59;P=0.001)、无进展生存时间(HR=1.65,95%CI:1.20~2.26;P=0.0019)及无复发生存时间(HR=1.70,95%CI:1.19~2.42;P=0.0029)均显著缩短。相比无RFC4基因改变组,RFC4基因变异组患者的预后更差(P<0.05)。富集分析结果显示,RFC4与其相关表达基因主要参与细胞周期、细胞分裂、DNA复制和修复等生物学过程。结论HCC中RFC4过度表达与预后相关,其可能是HCC潜在的预后生物标志物。Objective To explore the potential prognostic biomarker and clinical significance of replication factor C4(RFC4)in hepatocellular carcinoma(HCC).Methods Gene expression profiling(GEPIA),Oncomine,UALCAN,Human Protein Atlas(HPA)and Kaplan-Meier plotter were used to analyze the expression of RFC4 mRNA and protein in HCC and to explore the relationship between the expression and clinical pathological characteristics and prognosis.The gene mutation,copy number alterations,mRNA expression and prognosis of RFC4 in HCC were analyzed by cBioPortal database.The interaction between co-expressed genes and protein-protein was analyzed and visualized by String,Metascape database and Cytoscape software,and to predict their biological functions.Results As for normal tissue,RFC4 mRNA was significantly over-expressed in HCC(P=4.58×10-8).And the expression of RFC4 was correlated with lymph node metastasis,pathological stage and tumor differentiation grade.The overall survival(HR=1.81,95%CI:1.26-2.59;P=0.001),progression-free survival(HR=1.65,95%CI:1.20-2.26;P=0.0019)and recurrence free survival(HR=1.70,95%CI:1.19-2.42;P=0.0029)were significantly shorter in the RFC4 mRNA overexpression group than those in the low expression group.The gene alterations of RFC4 was significantly associated with poor overall survival and disease-free survival of HCC patients(P<0.05).The result of enrichment analysis of RFC4 and related genes indicated that they were mainly involved in the biological processes of cell cycle,cell division,DNA replication and DNA repair.Conclusion Over-expression of RFC4 is related to the prognosis of HCC,and it is a potential prognostic biomarker.

关 键 词：肝细胞癌 复制因子C 预后 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]