Reduced CCR2 Can Improve the Prognosis of Sarcoma by Remodeling the Tumor Microenvironment

Abstract

Background: The tumor microenvironment (TME) plays a very important role in the development of sarcoma (SARC), but it is still unknown how to effectively regulate the TME. Aim: Our study aims to identify core molecules that can concurrently regulate immune and stromal cells in TME as potential therapeutic targets. Methods and Results: We used the ESTIMATE algorithm to score the immune and stromal components of 265 SARC samples and determined that increased immune and stromal components in TME were both associated with poor prognosis in SARC. Next, we identified differential genes that regulate both immune and stromal cells, and identified the core prognostic gene CCR2 through the protein–protein interaction (PPI) network, COX analysis, survival analysis, and GSEA enrichment analysis. Next, we calculated the content of infiltrating immune cells and stromal cells in tumors using the CIBERSORT and xcell algorithms, respectively. Using differential analysis and Spearman correlation analysis, we identified 12 immune cells and 7 stromal cells, including CD4+T cells, CD8+T cells, monocytes, macrophages, dendritic cells, NK cells, mesenchymal stem cells (MSC), Fibroblasts and Endothelial cells, all of which were regulated by CCR2. Conclusion: Increased immune and stromal cell components were associated with poor prognosis in SARC, and CCR2 had a prognostic role in TME, regulating multiple immune and stromal cells, and was an important target for TME remodeling as well as immunotherapy in SARC.