Abstract
Simple SummaryFerroptosis is an iron-dependent cell death which is distinctive from common forms of cell death. Accumulating evidence indicated the close relationship between ferroptosis and numerous human diseases. Regarding breast cancer, a related study indicated that some targeted medicines could induce ferroptosis, furthermore, some basic research found that ferroptosis-related genes were closely related to breast cancer. However, the correlation between ferroptosis-related genes and breast cancer patients’ prognosis remains unknown. We built an 8-ferroptosis-related-gene model to predict breast cancer patients’ prognosis. This model could stratify patients into high- or low-risk groups. Additionally, tumor microenvironment analyses displayed differently enriched immune cells and immune pathways between these two groups. This 8-gene model is believed to be of great value in predicting prognosis for breast cancer patients.Breast cancer is the second leading cause of death in women, thus a reliable prognostic model for overall survival (OS) in breast cancer is needed to improve treatment and care. Ferroptosis is an iron-dependent cell death. It is already known that siramesine and lapatinib could induce ferroptosis in breast cancer cells, and some ferroptosis-related genes were closely related with the outcomes of treatments regarding breast cancer. The relationship between these genes and the prognosis of OS remains unclear. The data of gene expression and related clinical information was downloaded from public databases. Based on the TCGA-BRCA cohort, an 8-gene prediction model was established with the least absolute shrinkage and selection operator (LASSO) cox regression, and this model was validated in patients from the METABRIC cohort. Based on the median risk score obtained from the 8-gene model, patients were stratified into high- or low-risk groups. Cox regression analyses identified that the risk score was an independent predictor for OS. The findings from CIBERSORT and ssGSEA presented noticeable differences in enrichment scores for immune cells and pathways between the abovementioned two risk groups. To sum up, this prediction model has potential to be widely applied in future clinical settings.
Highlights
Breast cancer, as a global health concern, is the most common malignancy among women and ranks as the second leading cause for cancer-related death in women
Results in this study revealed 18 differently expressed ferroptosis-related genes between breast cancer tissue and normal tissue, and 3 out of them were of prognostic value
A previous study revealed that 3 ferroptosis-related genes (SLC7A11, G6PD, CISD1) in hepatocellular carcinoma were upregulated in tumor tissue, and their high expression correlated with a poor prognosis [15]
Summary
As a global health concern, is the most common malignancy among women and ranks as the second leading cause for cancer-related death in women. The five-year survival rate for breast cancer patients with stages III and IV were 57% and 23.4%, respectively [4]. It is commonly known that multigene signatures could provide risk stratification and prognostic prediction in breast cancer, such as PAM50 signature [5]. This kind of multigene signature brings insight to molecular biologic characteristics of breast cancer, as transcriptome or related molecular biologic data was the original source of constructing such a prognostic prediction model. This study aims to develop a ferroptosis-related gene signature to predict overall survival (OS) for breast cancer patients
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