Purpose: In the tumor microenvironment, the functional differences among various tumor-associated macrophages (TAM) are not completely clear. Tumor-associated macrophages are thought to promote the progression of
cancer. This article focuses on exploring M2 macrophage-related factors and behaviors of renal clear cell
carcinoma. Method: We obtained renal clear cell
carcinoma data from TCGA-KIRC-FPKM, GSE8050, GSE12606, GSE14762, and GSE3689. We used the "Cibersort" algorithm to calculate type M2 macrophage proportions among 22 types of immune cells. M2 macrophage-related co-expression module genes were selected using weighted gene co-expression network analysis (WGCNA). A renal clear cell
carcinoma prognosis risk score was built based on M2 macrophage-related factors. The ROC curve and Kaplan-Meier analysis were performed to evacuate the risk score in various subgroups. The Pearson test was used to calculate correlations among M2 macrophage-related genes, clinical phenotype, immune phenotype, and
tumor mutation burden (TMB). We measured differences in co-expression of genes at the
protein level in clear
renal cell carcinoma tissues. Results: There were six M2 macrophage co-expressed genes (F13A1, FUCA1, SDCBP, VSIG4, HLA-E, TAP2) related to infiltration of M2 macrophages; these were enriched in neutrophil activation and involved in immune responses, antigen processing, and presentation of exogenous
peptide antigen via MHC class I. M2-related factor frequencies were robust
biomarkers for predicting the renal clear cell
carcinoma patient clinical phenotype and immune microenvironment. The Cox regression model, built based on M2 macrophage-related factors, showed a close prognostic correlation (AUC = 0.78). The M2 macrophage-related prognosis model also performed well in various subgroups. Using western blotting, we found that VSIG4
protein expression levels were higher in clear
renal cell carcinoma tissues than in normal tissues. Conclusion: These co-expressed genes were most related to the M2 macrophage phenotype. They correlated with the immune microenvironment and predicted outcomes of renal clear cell
carcinoma. These co-expressed genes and the biological processes associated with them might provide the basis for new strategies to intervene via chemotaxis of M2 macrophages.