Abstract
BACKGROUND: Breast cancer continues to pose a significant global health burden, accounting for a substantial proportion of cancer-related mortality in women worldwide. Despite advancements in therapeutic strategies, overall survival rates remain suboptimal, underscoring the critical need for innovative prognostic tools to improve patient outcomes. METHODS: In this study, we introduced a novel tumor mitochondria transfer (TMT) scoring system based on 17 core genes to assess mitochondrial dynamics and their potential impact on the tumor microenvironment. Utilizing comprehensive datasets from TCGA-BRCA and GEO databases, we investigated the association between TMT scores and immune-metabolic features at both multi-cell and single-cell resolutions. Single-cell RNA sequencing (scRNA-seq) profiles were used to delineate the biological consequences of mitochondrial transfer. Additionally, co-culture experiments were conducted to validate our findings. RESULTS: Our analysis revealed that elevated TMT scores are strongly associated with adverse clinical outcomes in patients with breast cancer. Tumors with high TMT scores exhibited pronounced hypoxia, immune suppression, and metabolic reprogramming. Specifically, these tumors demonstrated impaired T-cell functionality and enhanced mitochondrial transfer to tumor cells, suggesting a pivotal role for mitochondrial dynamics in promoting immune evasion and metabolic adaptations that drive tumor progression. CONCLUSIONS: The TMT score may represent a novel prognostic biomarker in breast cancer, highlighting the intricate relationship between mitochondrial transfer and tumor pathophysiology. Our findings suggested that targeting mitochondrial dynamics could be a potential therapeutic avenue for exploration, which might enhance breast cancer management strategies. Further exploration of the mitochondrial mechanisms in cancer biology may pave the way for more precise and effective therapeutic interventions.