Profiles of ferroptosis-related genes and their prognostic values in patients with breast cancer brain metastasis

Abstract Background Ferroptosis is involved in various cancers. The role of ferroptosis in breast cancer brain metastasis (BCBM) is unclear. This study aimed to explore the ferroptosis-related genes (FRG) expression profiles in BCBM, as well as evaluate the FRG prognostic values in breast cancer patients.Methods Genes expression and clinical data were downloaded from Gene Expression Omnibus (GEO). Functional enrichment analysis was used to investigate the FRG bioinformatics functions. Univariate and multivariate cox regression analysis were performed to explore the independent prognostic factors. The correlation between ferroptosis and immunity was also evaluated. Finally, the FRG and their prognostic values were validated in external cohorts.Results Fourteen significantly different FRG were screened between breast cancer and BCBM tissues. GO and KEGG results showed FRG were enriched in the ferroptosis-related activities. Protein‑protein interaction (PPI) network analysis showed the HMOX1 and TFRC were hub genes. Survival analysis demonstrated HMOX1 and PEBP1 were significantly associated with overall survival (OS) (HR=2.100, P=0.035; HR=0.421, P=0.017 respectively). The KEAP1 and LPCAT3 had prognostic values for relapse-free survival (RFS) (HR=0.745, P=0.002; HR=2.536, P=0.008 respectively). Patients in high-risk group have worse OS and RFS compared with those in low-risk group (P=0.004, 0.021 respectively). Clinical correlation analysis revealed FRG were significantly associated with estrogen receptor (ER) status, progesterone receptor (PgR) status, HER2 and pathological grade in breast cancer patients (all P<0.05). In addition, we also found that immune-related pathways and immune status were different between high and low-risk groups. External cohort results showed FRG were significantly different between breast cancer and BCBM tissues. Survival validation demonstrated ALOX5 and CS were associated with prognosis in breast cancer patients (P=0.044, 0.032 respectively). Conclusions Our study identified the ferroptosis-related genes that may be involved in biology of BCBM, and FRG could serve as prognostic biomarkers in breast cancer patients. New therapy targeting ferroptosis holds probabilities for effective treatment in BCBM patients.