微小染色体维持蛋白3在脑胶质瘤中的表达及其临床意义

摘 要] 目的：分析微小染色体维持蛋白3（minichromosome maintenance protein 3，MCM3）在脑胶质瘤中的表达情况、临床意义和可能参与的生物学过程，并探究其与胶质瘤免疫的关系。方法：在线检索GEPIA和Oncomine数据库获得MCM3在胶质瘤组织中的表达情况，利用CGGA数据库在线分析MCM3表达和胶质瘤临床病理特征的关系。同时收集2019年1月到2020年3月在山西省人民医院神经外科接受手术治疗的24例胶质瘤患者的肿瘤标本和8例非肿瘤对照标本，采用免疫组化SP法检测MCM3的表达，对生物信息学分析结果进行验证。在TCGA和CGGA数据库中利用Kaplan-Meier生存曲线评价MCM3对胶质瘤预后的作用。通过Linkedomic数据库、STRING数据库和Cytoscape软件获得与MCM3表达显著相关的基因。使用DAVID数据库对MCM3及其显著相关基因进行GO和KEGG分析，探究基因功能。最后在TIMER数据库中探究MCM3表达和胶质瘤免疫浸润的关系。结果：综合生物信息学与临床数据分析显示，MCM3在胶质瘤组织中相对正常组织呈高表达（P=0.024），其表达量随着病理级别逐渐升高（P=0.001）。生存分析显示，MCM3高表达与胶质瘤不良预后有关（P＜0.05）。GO和KEGG分析显示，MCM3及其显著相关基因主要富集于细胞周期、DNA复制和调节DNA损伤修复等方面。TIMER数据库分析结果显示，在胶质瘤队列中，MCM3与多种免疫浸润细胞具有相关性（P＜0.05）。结论：MCM3在胶质瘤中高表达且与不良预后有关，其可能与胶质瘤细胞的细胞周期、DNA复制、调节DNA损伤修复和免疫微环境有关。MCM3能促进胶质瘤的进展，可作为胶质瘤患者预后判断指标和潜在的治疗靶点。

The expression of minichromosome maintenance protein 3 in brain glioma and its clinical significances

Abstract] Objective: Analyze the expression, clinical significance and possible biological processes of minichromosome maintenance protein 3 (MCM3) in brain gliomas, and explore its relationship with glioma immunity. Methods: The databases GEPIA and Oncomine were searched online to obtain the expression of MCM3 in glioma tissues. The CGGA database was used to analyze the relationship between MCM3 expression and clinicopathological characteristics of gliomas online.At the same time, 24 tumor specimens of patients with glioma who underwent surgical treatment in the Department of Neurosurgery of Shanxi Provincial People''s Hospital from January 2019 to March 2020 and 8 non-tumor control specimens were collected, and used immunohistochemical SP method to detect the expression of MCM3 to verify the bioinformatics analysis results. Kaplan-Meier survival curve was used to evaluate the effect of MCM3 on the prognosis of glioma in the TCGA and CGGA databases.The significant related genes of MCM3 were obtained through Linkedomic database, STRING database and Cytoscape software. Use the DAVID database to perform GO and KEGG analysis of MCM3 and its significant related genes to explore the biological processes they may participate in.Finally, explore the relationship between MCM3 expression and glioma immune infiltrating cells in the TIMER database. Results: Comprehensive bioinformatics analysis and clinical data verification showed that MCM3 was highly expressed in glioma tissues relative to normal tissues (P=0.024), and its expression level gradually increased with the pathological grade (P=0.001).Survival analysis showed that high expression of MCM3 was related to the poor prognosis of glioma (P<0.05).GO and KEGG analysis of MCM3 and its significant related genes showed that these genes are mainly enriched in cell cycle, DNA replication and regulation of DNA damage repair.TIMER database showed that in the glioma cohort, MCM3 was correlated with a variety of immune infiltrating cells (P<0.05). Conclusions: MCM3 is highly expressed in gliomas and is related to poor prognosis, which may be related to the cell cycle, DNA replication, regulation of DNA damage repair and immune microenvironment of glioma cells. MCM3 can promote the progression of glioma, and can be used as a prognostic indicator and potential therapeutic target for patients with glioma.