Comprehensive analysis of ACKR family members in breast cancer using prognostic values.

Breast cancer (BC) is by far the most prevalent malignancy found in the female population. Atypical chemokine receptors (ACKRs) are a subclass of G-protein-coupled receptors, which are characterized by disrupted ligand binding and a breakdown of signaling following ligand binding. The evolution and function of multiple ACKRs in BC have yet to be fully elucidated, although certain findings on this family have been reported in several studies in and other species. The present study identified that the expression level of ACKRs was significantly lower in breast carcinoma (BRCA) tissues compared with normal breast tissues through searches of the Tumor Immune Estimation Resource, UALCAN and Gene Expression Profiling Interactive Analysi databases. Additionally, when comparing BRCA tissues with normal breast tissues, it was found that there was obvious hypomethylation in the promoters of and , as well as a marked hypermethylation in the promoters of and In determining the prognosis of patients with BRCA, the expression levels of ACKR1, ACKR2, ACKR3, ACKR4 and ACKR6 were all found to be important factors. The values for distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) were all found to be lower in patients with BRCA who had a low expression level of ACKR1. In addition, the RFS rates for patients with BRCA were lower when the expression of ACKR2 was low, and worse values for DMFS, OS and RFS were found to be highly correlated with higher expression levels of ACKR3. Moreover, the DMFS, OS, RFS and predictive power score values were worse in those patients with low ACKR4 expression, and the RFS values for patients with BRCA were also found to be lower when the expression level of ACKR6 was low. Additionally, dendritic cells, macrophages, neutrophils, T cells with CD4 status, T cells with CD8 status and B cells were all substantially linked with ACKR expression, as well as immune cell infiltration. Taken together, the findings of the present study may offer a theoretical foundation for the creation of novel targets and prognostic indicators for BRCA therapy.