Identification of macrophage related gene in colorectal cancer patients and their functional roles

Abstract

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.

E2F3 renders an immunosuppressive tumor microenvironment in nasopharyngeal carcinoma: Involvements of the transcription activation of PRC1 and BIRC5

“… 32 The PRC1 has also been identified as one of the hub macrophage‐related genes in colorectal cancer patients. 33 As for BIRC5, similarly, it is reportedly expressed at particularly high levels in prostate tumors characterized by infiltration of TAMs, suggesting its potential correlation with TAM infiltration. 18 We therefore wondered whether PRC1 and BIRC5 participate in the maintenance of M2 TAMs in the TME of NPC as well.…”

“…In hepatocellular carcinoma, likewise, high PRC1 expression has been linked to increased TAM infiltration and poor prognosis of patients 32 . The PRC1 has also been identified as one of the hub macrophage‐related genes in colorectal cancer patients 33 . As for BIRC5, similarly, it is reportedly expressed at particularly high levels in prostate tumors characterized by infiltration of TAMs, suggesting its potential correlation with TAM infiltration 18 .…”

Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population

“…NIT2 , identified as ω-amidase, plays an important metabolic role by catalyzing hydrolysis of α-ketoglutaramate and α-ketosuccinamate, yielding α-ketoglutarate and oxaloacetate, respectively 18 , 19 . Some studies have shown that the overexpression of NIT2 is related to the occurrence and development of colon cancer 20 , 21 and tongue squamous cell carcinoma 22 . In colon cancer, the downregulation of NIT2 inhibits the proliferation of colon cancer cells and induces cell cycle arrest through the caspase-3 and PARP pathways.…”