Oxeiptosis gene expression profiling identified TCN1 as a prognostic factor for breast cancer

Abstract Objectives Oxeiptosis could suppress the progression of breast cancer (BRCA). We aim to identify the prognostic factor associated with BRCA using oxeiptosis gene expression profiling and investigate its role in BRCA. Methods We extracted RNA sequencing data and clinical information on BRCA samples from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases using an oxeiptosis-related gene set. Prognosis-related genes for BRCA were screened from the TCGA dataset using bioinformatics analysis. Subsequently, we constructed a prognostic model for BRCA depending on the expression of this predictive factor and analyzed the associated function. The effects of Transcobalamin 1 (TCN1) on BRCA cell function and H 2 O 2 -induced oxeiptosis were validated in vitro . Results TCN1 was identified as the most strongly associated factor with BRCA prognosis among the differentially expressed genes in oxeiptosis. Patients with high TCN1 expression demonstrated a better prognosis in BRCA. In BRCA, TCN1 was enriched in response to the oxidative stress pathway. Additionally, TCN1 was associated with the expression of immune checkpoints and gene variations. Compared to normal human breast epithelial cells, TCN1 was downregulated in BRCA cells. Overexpression of TCN1 inhibited the proliferation, migration, and invasion of BRCA cells, and enhanced H 2 O 2 -induced oxeiptosis in BRCA cells. Conclusions Based on the oxeiptosis gene set, we identified TCN1 as a prognostic factor associated with BRCA. The findings highlight the potential of TCN1 as a therapeutic target and provide valuable insights into the development of personalized treatment strategies for BRCA.