Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

Abstract

Objective: Colorectal cancer (CRC) is one of the most common malignancies worldwide. MCM7 is one of the important components of DNA replication complex involved in cancer progression. At present, the significance of MCM7 and its mechanisms in CRC development are still unclear. Materials and Methods:Gene expression data of CRC was downloaded from Gene Expression Omnibus (GEO) and TCGA databases. Bioinformatics method was applied to screen CRC differentially expressed genes (DEGs). MCODE and degree value analysis were used to select core genes. The datasets were explored to verify the mRNA expression level of MCM7, and the protein expression level of MCM7 was further verified by Western Blotting and immunohistochemical analysis. Moreover, we also analyzed the correlation between MCM7 and clinical characteristics. The prognostic value of MCM7 in CRC was explored through Kaplan-Meier analysis, univariate and multivariate Cox regression analysis. Results:We confirmed that MCM7 was up-regulated in CRC tissues compared with adjacent non-tumor tissues. MCM7 overexpression was positively associated with lymph node metastasis and TNM stage in CRC. Higher expression of MCM7 showed shorter overall survival rate. Furthermore, MCM7 level could be an independent prognostic factor for CRC. Conclusion:Our study suggested that MCM7 may be a new prognostic factor or molecular target in CRC.The R package 'edgeR' and'limma' were applied to identify the DEGs between CRC tissues and normal tissues. The inclusion standard of DEGs from TCGA was adjusted P <0.01 and log2 Fold Change (FC)>2. DEGs from GEO datasets were selected with the criterion of combined adjusted p< 0.01 and log2FC >1 or log2FC>0.58. Protein-protein interaction (PPI) network construction and module analysisSTRING (https://string-db.org) was applied to construct PPI network for DEGs with confidence score>0.4 and p<0.01. Cytoscape software was used to visualize network. Another, the Molecular Complex Detection (MCODE) app was used to screen modules of PPI network in Cytoscape under degree cutoff =2, node score cutoff=0.2, k-core=2, and max.depth=100. Moreover, the nodes were calculated the degree value.