基于生物信息学分析MCM8基因在胃癌组织中的表达及临床意义

Expression of MCM8 gene in gastric cancer and its clinical significance by bioinformatics analysis

目的:分析MCM8基因在胃癌和癌旁组织中的表达差异,探讨其与胃癌临床病理特征、肿瘤免疫浸润水平、预后的相关性及其可能的调控网络。方法:利用GEO、TCGA数据库分析MCM8基因在胃癌和癌旁组织中的表达差异,并收集30例临床组织标本进行免疫组化染色进一步验证其在蛋白水平的表达差异;通过UALCAN与Kaplan-Meier Plotter数据库分析MCM8基因与胃癌患者临床病理学参数及预后的关系;通过TISIDB数据库分析MCM8与胃癌肿瘤免疫浸润水平的关系;基于cBio-Portal工具调取TCGA数据库中胃癌患者MCM8的共表达基因,并进行GO聚类分析及蛋白-蛋白相互作用网络分析。结果:胃癌组织中MCM8的mRNA及蛋白表达丰度显著升高;MCM8高表达的胃癌患者总体生存率显著降低;胃癌患者中MCM8表达量与其肿瘤微环境中的活化CD8^(+)T细胞、B细胞、NK细胞、树突状细胞表达丰度负相关;GO聚类分析及蛋白相互作用网络分析显示MCM8蛋白可能参与调控细胞周期、DNA错配修复等生物学进程,并与POLA1、ORC1、CDC7、CDC45等分子密切相关。结论:MCM8与胃癌患者的恶性临床病理特征、不良预后及肿瘤免疫浸润水平密切相关,可作为一个良好的胃癌诊断、预后评估的生物学标志物。

Objective:To analyze the differential expression of MCM8 gene in gastric cancer and adjacent normal tissues,explore its correlations with clinicopathological characteristics,tumor-infiltrating immune levels and prognosis of gastric cancer,and to explore its possible regulatory networks.Methods:The differential expression of MCM8 gene in gastric cancer and adjacent normal tissues were analyzed using GEO and TCGA databases,meanwhile,30 clinical tissue specimens were collected for further verification at the protein level by immunohistochemical staining. UALCAN and Kaplan-Meier Plotter databases were used to analyze the relationships between MCM8 expression and clinico-pathological parameters,clinical prognosis of patients with gastric cancer. Correlations between MCM8 expression and cancer immunal infiltrations was investigated via TISIDB database. cBio-Portal tool was used to analyze the CO-expression network of MCM8 gene in TCGA gastric cancer,GO enrichment analysis and protein-protein interaction analysis were performed on the basis of the CO-expression network.Results:MCM8 gene was overexpressed in gastric cancer tissues both at the mRNA and protein level,and MCM8 expression was associated with a significantly short overall survival rate. MCM8 expression was negatively correlated with infiltrating levels of CD8^(+)T cells,B cells,NK cells,dendritic cells in gastric cancer,while it was positively correlated with the expression of CD4^(+)T cells. The protein-protein interaction network analysis revealed that MCM8 was closely related to POLA1,ORC1,CDC7 and CDC45. GO enrichment analysis showed that MCM8 played potential roles in the regulation of cell cycle,DNA mismatch repair and other biological processes. Conclusion:MCM8 showed strong correlations with the malignant clinico-pathological characteristics,poor prognosis and tumor immune infiltration levels of gastric cancer,and it may be act as a potential biomarker for the diagnosis and prognosis assessment of gastric cancer.