Taxanes are first-line chemotherapeutic agents for patients with triple-negative breast cancer (TNBC). However, resistance, the main cause of clinical treatment failure and poor prognosis, reduces their effectiveness and has become an increasingly important problem. Recently, a form of iron-dependent programmed cell death called ferroptosis was reported to play an important role in regulating tumor biological behavior. In this study, we revealed the prognostic significance of the ferroptosis‑related gene (FERG) model and clarified that ferroptosis-related genes may be promising candidate biomarkers in cancer therapy. First, resistance-related FERGs were screened, and univariate Cox regression analysis was used to construct a prognostic model, including GRIK3, IDO1, and CLGN. Then, the patients with TNBC in the TCGA database were classified into high-risk and low-risk groups. The identification of TNBC in the TCGA database revealed that patients with high scores had a higher probability of dying earlier than those with low scores. Moreover, these three genes were associated with immune infiltrates and checkpoints in TNBC patients. In conclusion, this study suggested that FERGs are significantly associated with chemotherapy resistance in patients with TNBC and that these genes can be used as prognostic predictors in these patients and possibly for targeted therapy in the future.

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.

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