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。
关键词：肝癌；MCMs；生物信息学；预后分析；作用机制
中图分类号：R735.7                               文献标志码：A                   DOI：10.3969/j.issn.1007-7146.2022.05.012

Abstract: 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.
Key words: hepatic celluler cancer; MCMs; bioinformatics; prognostic analysis; mechanism of action
（Acta Laser Biology Sinica, 2022, 31(5): 471-480）