Integrative multi-omics analysis reveals UBE2C as a potential prognostic biomarker and therapeutic target of breast cancer.

Breast cancer remains one of the leading causes of cancer-related mortality among women globally, underscoring the need for novel therapeutic targets. In this study, we identify Ubiquitin-Conjugating Enzyme E2 C (UBE2C) as a key regulator of tumor progression and therapeutic vulnerability in breast cancer. An integrated pan-cancer analysis reveals that UBE2C is significantly overexpressed in breast cancer and is associated with adverse clinical outcomes across various malignancies. Furthermore, single-cell analyses demonstrate that UBE2C enhances tumor proliferation through its regulation of cell cycle progression. Mechanistically, we establish Forkhead Box M1 (FOXM1) as the potential transcriptional regulator of UBE2C, evidenced by its specific binding to the UBE2C promoter and a conserved co-expression pattern across different cancers. Importantly, our findings predicted a synthetic lethal interaction between UBE2C and FOXM1, suggesting that concurrent inhibition of this pathway results in synergistic anticancer effects. This study identifies the FOXM1-UBE2C axis as a novel synthetic lethal pathway in breast cancer, offering potential as both a potential prognostic biomarker and a therapeutic target.