Integrated analysis reveals prognostic correlation and immune characteristics of a tumor-associated macrophage-based risk signature in triple-negative breast cancer.

Abstract

Background: Tumor-associated macrophages play a critical role in the progression and immune response of triple-negative breast cancer (TNBC). Our study aimed to explore the characteristics of tumor-associated macrophages (TAMs) in TNBC, construct a risk signature associated with TAM clusters, and verify its relationship with prognosis and immune-related characteristics.

Methods: Firstly, we identified four TAM clusters and determined prognosis-related clusters in TNBC based on the single-cell RNA sequencing (scRNA-seq) data. Subsequently, the TAM-related prognostic genes were obtained by the univariate Cox regression analysis and an 8-gene risk signature was then constructed by least absolute shrinkage and selection operator (LASSO) regression based on these TAM-related prognostic genes. Analyses of immune characteristics showed a significant association between the signature with stromal and immune scores, as well as some immune cells.

Results: Multivariate analysis revealed that the risk signature was an independent prognostic factor for TNBC, and its value in predicting immunotherapeutic outcomes was also confirmed. A novel nomogram integrating the stage and TAM-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of TNBC. Finally, the increasing expression of GPR34 which is one of the eight hub genes was explored in TNBC by experiments including reverse-transcriptase polymerase chain reaction, western blot, and immunohistochemistry.

Conclusions: Our study may provide unique insights into obtaining independent prognostic factors, improving immunotherapeutic strategies, and identifying effective therapeutic targets for TNBC.