A Novel Ferroptosis-Related Gene Signature for Chemotherapy Resistance Prediction in Triple-negative Breast Cancer

Abstract 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.