Single-cell analysis reveals that MXRA8 affected the progression of breast cancer via regulating ferroptosis.

Breast cancer is one of the most prevalent malignant tumors among women worldwide. The incidence of breast cancer in China has been steadily increasing, posing a significant public health concern that gravely jeopardizes women's well-being. Given the heterogeneity and drug resistance associated with breast cancer, conventional treatment methods are inadequate to meet current therapeutic demands, necessitating the urgent development of new biomarkers and therapeutic targets. Ferroptosis, characterized by iron-dependent lipid peroxidation-induced cell membrane rupture, represents a form of programmed cell death. As ferroptosis gains increasing attention for its role in cancer biology, its potential value as an anti-cancer therapy is being gradually explored. However, our understanding of tumor cell ferroptosis in breast cancer remains incomplete, particularly at the single-cell level where knowledge is limited. Therefore, delving into the heterogeneous response of breast cancer cells to ferroptosis and elucidating its regulatory mechanisms hold great significance for comprehending the biological behavior of breast cancer and devising novel therapeutic strategies. In this study, we reanalyzed single-cell RNA-seq data from 26 breast cancer patients using a non-negative matrix (NMF) algorithm. GSEA enrichment analysis was employed to identify tumor subsets most susceptible to ferroptosis while pseudotiming was utilized to pinpoint MXRA8 as a key gene regulating ferroptosis. CellChat was applied to explore relationships between different subsets and various immune cell populations. Finally, we conducted in vitro experiments to validate MXRA8's involvement in regulating ferroptosis in cancer cells. This study unveils the crucial role played by ferroptosis-related tumor subsets in breast cancer progression and tumor immunity.