Identification of colorectal cancer-associated macrophage biomarkers by integrated bioinformatic analysis

The aim of this study was to explore colorectal tumor-associated macrophage (TAM) biomarkers for early diagnosis and surveillance of colorectal cancer (CRC). We used bioinformatic methods to screen array expression data of CRC-related macrophages (GEO: GSE29214) to detect the differentially expressed genes (DEGs) between CRC-related macrophages and normal control cells. We found 431 DEGs in TAMs compared with the control group; 399 were up-regulated and 32 were down-regulated. A functional enrichment analysis showed that the DEGs were involved in positive regulation of the ERK1 and ERK2 cascade, cell activation involved in the immune response, cytokine-mediated signaling pathway, and receptor activity, all of which were significantly enriched. We constructed a protein-protein interaction (PPI) network to identify hub genes. We identified 10 hub genes: ITGB2, ITGAM, C3AR1, PTAFR, C3, CYBB, FCER1G, PLAU, STOM, and GPR84, in the PPI network. We verified the results using array expression data of peripheral blood mononuclear cells (GEO: GSE47756). The results showed that the expression trends of CYBB, PLAU, and STOM were consistent with those found in the GSE29214 dataset. Further verification with The Cancer Genome Atlas and Human Protein Atlas showed that the high expression of PLAU in TAMs was statistically significant (P<0.05). We concluded that PLAU may be a biomarker of CRC-associated macrophages and may have prognostic and predictive significance for clinical utility in CRC management.