Prognostic correlation and immune characteristics of a TAM cluster- related 8-gene risk signature in triple-negative breast cancer

Abstract Tumor-associated macrophages (TAMs) play a critical role in the progression of and immune response to triple-negative breast cancer (TNBC). This study aimed to explore the features of TAMs in TNBCs, construct a risk signature associated with TAM clusters, and verify their relationship with prognosis and immune-related characteristics. Primarily, we selected four TAM clusters and determined the prognosis-related clusters in TNBC based on single-cell RNA sequencing data. Subsequently, TAM-related prognostic genes were identified by univariate Cox regression analysis and an 8-genes risk signature was constructed by LASSO regression. The analysis of immune characteristics showed a significant association between the gene signature and stromal and immune scores as well as immune cells. Multivariate analysis revealed that the risk signature was an independent prognostic factor for TNBC, and confirmed its predictive value for immunotherapeutic outcomes. The newly constructed nomogram integrating stage and TAM-based risk signatures exhibited favorable predictability and reliability for TNBC prognosis prediction. Finally, the increased expression of GPR34, one of the eight hub genes, was explored in TNBC using reverse-transcriptase polymerase chain reaction, western blot, and immunohistochemistry. Our study may allow discovering new independent prognostic factors, updating immunotherapeutic methods, and identifying effective therapeutic targets for TNBC.