Bioinformatic Analysis of the Expression and Clinical Significance of the DNA Replication Regulator MCM Complex in Bladder Cancer

Ru Chen,1,2,* Bing Hu,1,* Ming Jiang,1,* Wen Deng,1 Ping Zheng,3 Bin Fu1,4 1Department of Urology, the First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Urology, The First Hospital of Putian City, Putian, Fujian, People’s Republic of China; 3Department of Urology, Shangrao municipal Hospital, Shangrao, 334000, Jiangxi Province, People’s Republic of China; 4Jiangxi Institute of Urology, Nanchang City, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Fu, Email urofbin@163.comObjective: The minichromosome maintenance (MCM) complex (MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7), which regulates DNA replication and cell cycle progression, is essential for the development and progression of multiple tumors, but their role in bladder cancer development remains unclear. In the present study, the biological role and clinical significance of the MCM complex in bladder cancer were systematically elucidated.Materials and Methods: We analyzed DNA mutations, mRNA expression and protein levels, protein–protein interaction (PPI) networks, functional enrichment, prognostic value of MCM2/3/4/5/6/7 in bladder urothelial carcinoma (BLC) and the connections between the immune cell infiltration and the overall survival of BLC patients with the MCM expression levels using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), the Cancer Genome Atlas database (TCGA), Human Protein Atlas, UALCAN, STRING, cBioPortal, TIMER and GSCALite databases.Results: The outcomes showed that the mRNA expression level of each member of the MCM complex was significantly correlated with histologic grade and tumor histology in BLC patients. Moreover, survival analysis showed that MCM/2/3/4/5/6/7 mRNA expressions were significantly associated with prognosis in patients with bladder cancer. Moreover, we experimentally validated the overexpression of the MCM2-7 complex in the BLC. Based on functional enrichment and PPI network analysis, the MCM complex might promote the progression of bladder cancer by activating DNA replication and accelerating cell cycle progression. In addition, MCM2/3/4/5/6/7 genes were also significantly associated with tumor immune cells infiltration and the drug sensitivity in BLC.Conclusion: Our study suggests that the MCM complex especially MCM2/4/6/7 might be potential molecular therapeutic targets for BLC treatment and might be useful biomarkers for diagnosis and prognosis.Keywords: bladder cancer, minichromosome maintenance complex, bioinformatics, potential biomarkers