Zheng Ruinian, Lai Guowei, Li Rongfa, Hao Yanyan, Cai Limin, Jia Jun
Department of Oncology, Dongguan Institute of Clinical Cancer Research, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, China.
Department of General Surgery, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, China.
J Gastrointest Oncol. 2021 Feb;12(1):153-173. doi: 10.21037/jgo-20-574.
The minichromosome maintenance (MCM) protein complex is important for DNA replication. Moreover, the expression of specific MCM complex components has been associated with the survival of hepatocellular carcinoma (HCC) patients. However, the expression and functional roles of minichromosome maintenance complex component 4 (MCM4) in HCC development and progression have not yet been explored. We analyzed the expression and clinical significance of MCM4, including its association with liver cancer patient survival.
Oncomine, UALCAN, and HCCDB (a database of HCC expression atlas) were used to characterize the expression of MCM4 in tumor and normal tissues. The expression of MCM4 at the protein level was confirmed based on immunohistochemistry (IHC) data obtained from the Human Protein Atlas (HPA) database. The level of MCM4 was measured in tumor and adjacent normal tissues by RT-qPCR, western blot and IHC staining. The copy number alterations (CNAs) and mutations in MCM4 were analyzed by cBioPortal, whereas the co-expression genes of MCM4 in HCC were obtained from Oncomine, and used for gene ontology and pathway analysis via the NetworkAnalyst 3.0 tool, to explore the predictive signaling pathway in HCC.
The levels of MCM4 messenger (m)RNA and protein were found to be significantly higher in liver cancer tissues than in normal liver tissues. Kaplan-Meier analysis showed that the upregulation of MCM4 was significantly negatively correlated with the survival of HCC patients.
Our data suggest that MCM4 may be used as a potential prognostic marker and therapeutic target for HCC.
微小染色体维持(MCM)蛋白复合物对DNA复制至关重要。此外,特定MCM复合物组分的表达与肝细胞癌(HCC)患者的生存相关。然而,微小染色体维持复合物组分4(MCM4)在HCC发生发展中的表达及功能作用尚未得到探索。我们分析了MCM4的表达及其临床意义,包括其与肝癌患者生存的关联。
利用Oncomine、UALCAN和HCCDB(HCC表达图谱数据库)来表征MCM4在肿瘤组织和正常组织中的表达。基于从人类蛋白质图谱(HPA)数据库获得的免疫组织化学(IHC)数据,证实了MCM4在蛋白水平的表达。通过RT-qPCR、蛋白质印迹和IHC染色测量肿瘤组织和相邻正常组织中MCM4的水平。通过cBioPortal分析MCM4的拷贝数改变(CNA)和突变,而从Oncomine获得HCC中MCM4的共表达基因,并通过NetworkAnalyst 3.0工具用于基因本体论和通路分析,以探索HCC中的预测信号通路。
发现肝癌组织中MCM4信使(m)RNA和蛋白质水平显著高于正常肝组织。Kaplan-Meier分析表明,MCM4的上调与HCC患者的生存显著负相关。
我们的数据表明,MCM4可能作为HCC的潜在预后标志物和治疗靶点。