Background: Recent scientific research has enabled the identification of macrophages related-genes (MaRG), which play a key role in the control of the immune microenvironment in many human cancers. However, the functional role of MaRGs in human tumors is ill-defined. Herein, we aimed at bioinformatically exploring the molecular signatures of MaRGs in colorectal cancer.
Methods: A list of MaRGs was generated and their differential expression was analyzed across multiple datasets downloaded from the publicly available functional genomics database Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) was also applied to identify the partner genes of these MaRGs in colorectal cancer.
Results: After integration of the results from analyses of different datasets, we found that 29 differentially expressed MaRGs (DE-MaRGs) could be considered as CRC-related genes as obtained from the WGCNA analysis. These genes were functionally involved in positive regulation of DNA biosynthetic process and glutathione metabolism. Protein-protein interaction network analysis indicated that PDIA6, PSMA1, PRC1, RRM2, HSP90AB1, CDK4, MCM7, RFC4, and CCT5 were the hub MaRGs. The LASSO approach was used for validating the 29 MaRGs in TCGA-COAD and TCGA-READ data and the results showed that ten among the 29 genes could be considered as MaRGs significantly involved in CRC. The maftools analysis showed that MaRGs were mutated at varying degrees. The nomogram analysis indicated the correlation of these MaRGs with diverse clinical features of CRC patients.
Conclusions: Conclusively, the present disclosed a signature of MaRGs as potential key regulators involved in CRC pathogenesis and progression. These findings contribute not only to the understanding of the molecular mechanism of CRC pathogenesis but also to the development of adequate immunotherapies for CRC patients.
Keywords: Colorectal cancer; Macrophage-related genes; Macrophages.