Abstract
IntroductionBreast cancer is the most common malignant tumor in women worldwide. However, advanced multidisciplinary therapy cannot rescue the mortality of high-risk breast cancer metastasis. Ferroptosis is a newly discovered form of regulating cell death that related to cancer treatment, especially in eradicating aggressive malignancies that are resistant to traditional therapies. However, the prognostic value of ferroptosis-related gene in breast cancer remains unknown.Materials and MethodsIn this study, a total of 1,057 breast cancer RNA expression data with clinical and follow-up information were downloaded from the TCGA cohort, multivariate Cox regression was used to construct the 11-gene prognostic ferroptosis-related gene signature. The breast cancer patients from the GEO cohort were used for validation. The expression levels of core prognostic genes were also verified in erastin-treated breast cancer cell lines by real-time polymerase chain action (PCR).Results and DiscussionOur results showed that 78% ferroptosis-related genes were differentially expressed between breast cancer tumor tissue and adjacent non-tumorous tissues, including 29 of them which were significantly correlated with OS in the univariate Cox regression analysis. Patients were divided into high-risk group and low-risk group by the 11-gene signature. Patients with high-risk scores had a higher probability of death earlier than the low-risk group both in the TCGA construction cohort and in the GEO validation cohort (all P < 0.001). Meanwhile, the risk score was proved to be an independent predictor for OS in both univariate and multivariate Cox regression analyses (HR > 1, P < 0.01). The predictive efficacy of the prognostic signature for OS was further verified by the time-dependent ROC curves. Moreover, we also enriched many immune-related biological processes in later functional analysis; the immune status showed a statistical difference between the two risk groups. In addition, the differences in expression levels of 11 core prognostic genes were examined in ferroptosis inducer-treated breast cancer cell lines.ConclusionIn conclusion, a novel ferroptosis-related gene model can be used for prognostic prediction in breast cancer. New ferroptosis-related genes may be used for breast cancer targeting therapy in the future.
Highlights
Breast cancer is the most common malignant tumor in women worldwide
After the identification of prognostic ferroptosis-related differentially expressed genes (DEGs) in the The Cancer Genome Atlas (TCGA) cohort, results showed that most of the ferroptosis-related genes (202/259, 78%) were differentially expressed between breast cancer tumor tissues and adjacent non-tumorous tissues, including 29 of them which were significantly correlated with overall survival (OS) in the univariate Cox regression analysis (Figure 2A)
A total of 29 prognostic ferroptosis-related DEGs were identified by the criteria of false discovery rate (FDR) < 0.05 (Figures 2B,C)
Summary
Breast cancer is the most common malignant tumor in women worldwide. Breast cancer is the most common malignant tumor in women worldwide; among 70–80% patients with early, non-metastatic disease can be cured. Under the joint multidisciplinary diagnosis and treatment model of surgery, radiotherapy, chemotherapy, endocrinology, and targeted precision therapy, the mortality of advanced breast cancer or high-risk breast cancer with metastasis has not been significantly improved (Emens, 2018). All these data highlight the additional need for innovative methods to identify patients with high-risk disease
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