微小染色体家族在肝癌中的表达和预后价值及其作用机制  

Expression and Prognostic Value of Microchromosomal Families in HCC and Its Mechanism of Action

作　　者：尹清臣[1] 王磊[1] 王景梅[1] 侯丽艳[1] 贾如江[1] YIN Qingchen;WANG Lei;WANG Jingmei;HOU Liyan;JIA Rujiang(The First Department of General Surgery,Handan Central Hospital,Handan 056102,China)

机构地区：[1]邯郸市中心医院普一科,邯郸056102

出　　处：《激光生物学报》2022年第5期471-480,共10页Acta Laser Biology Sinica

基　　金：河北省卫健委重点科技研究计划项目(20200449)。

摘　　要：本研究通过生物信息学工具分析微小染色体家族(MCMs)在肝癌中的表达,结果显示,肝癌组织MCMs基因及其蛋白的表达明显升高,差异有统计学意义(P<0.05)。MCMs基因在Ⅰ、Ⅱ、Ⅲ期肝癌中随着分期升高表达明显升高,差异有统计学意义(P<0.05),MCM2、MCM3、MCM5、MCM6、MCM7基因表达水平与肝癌患者的无病生存率(DFS)、总生存率(OS)显著相关(P<0.05)。高表达MCMs的肝癌患者总生存期较差,MCMs表达具有明显相关性。利用String-DB数据库进行蛋白网络互作模型分析,与MCMs具有相互作用的蛋白包括MCM10、ORC1、ORC2、ORC4、ORC5、GINS1、GINS2、GINS3、GINS4、CDC6、CDC7、CDC45、ASF1B、CDT1、WDHD1等。利用Metascape进行信号通路富集分析显示,MCMs主要富集在DNA复制、细胞周期调节、DNA依赖的DNA复制、复制前体复合物的活化、DNA解螺旋、核基因的复制、DNA调控的复制、CDC6相关的起始识别复合物的调节、DNA复制检查点的调控、蛋白-DNA复合物的组装等信号通路。研究认为,MCMs在肝癌组织中呈现高表达,与患者预后显著相关,MCMs表达具有明显相关性,在肝癌中MCMs主要干扰DNA合成、复制的具体过程,从而导致肝癌的发生发展。本研究为肝癌精准治疗提供了新的方向。The expressions of MCMs genes in hepatocellular carcinoma were analyzed based on bioinformatics.The expressions MCMs genes and proteins in HCC were significantly higher than those in normal hepatic tissue(P<0.05).The expressions of MCMs genes increased significantly with the increase of the stage of HCC(P<0.05).Expressions level of MCM2,MCM3,MCM4,MCM5,MCM6,MCM7 were significant correlation with disease-free survival(DFS)and overall survival(OS)(P<0.05).Patients with high expression of MCMs genes had poorer DFS and overall OS.We further found those proteins that interact with MCMs include MCM10,ORC1,ORC2,ORC4,ORC5,GINS1,GINS2,GINS3,GINS4,CDC6,CDC7,CDC45,ASF1B,CDT1,WDHD1.Metacape signals pathway enrichment analysis showed that MCMs genes were mainly enriched in DNA replication,cell cycle regulation,DNA-dependent DNA replication,activation of replication precursor complex,DNA uncoiling,nuclear gene replication,DNA-regulated replication,CDC6-related initial recognition complex regulation,DNA replication checkpoint regulation,protein-DNA complex assembly and other signal pathways.MCMs were highly expressed in HCC,which were significantly associated with patient prognosis.MCMs expressions showed a clear correlation.MCMs mainly interferes with DNA synthesis and replication,leading to the occurrence and development of HCC.

关 键 词：肝癌 MCMs 生物信息学 预后分析 作用机制 

分 类 号：R735.7[医药卫生—肿瘤]