The role of CCR2 in prognosis of patients with endometrial cancer and tumor microenvironment remodeling.

Abstract

Tumor microenvironment (TME) plays a core role in the genesis and progress of endometrial carcinoma (EC). The immune system, a crucial element of TME, functions in various immune cells. In this paper, we have tried to evaluate the prognosis in EC patients by the status of TME. The ESTIMATE algorithm was implemented to computer the number of immune and stromal components in EC tissues from the Cancer Genome Atlas dataset. The CIBERSORT algorithm was employed to assess the proportion of tumor-infiltrating immune cells in EC tissues, which were quantified as Stromal score and Immune score. After the construction of protein-protein interaction network, cell-cell chemokine receptor 2 (CCR2) was identified as a potential predictive element for EC. Further analysis indicated that a higher expression of CCR2 in EC patients was correlated with a better prognosis and a prolonged disease-free survival. According to the transcript level of CCR2, samples were separated into low- and high-expression groups. Gene Set Enrichment Analysis unveiled that metabolism-related pathways were mostly abundant in groups with high-expression, the other one was primarily correlated to immune-related activities. We figured out that some immune cells were positively related to CCR2, suggesting that CCR2 might serve as the immune-dominant status of TME, which was verified by qRT-PCR and HPA analysis in transcriptome and protein level, respectively. Also, CCR2 showed high correlation with immune modulators and chemokine signaling pathway. Thus, the level of CCR2 might have a prognostic value for EC patients, which provides a novel insight for therapeutic strategies of EC.