Development of coenzyme Q10-related molecular subtypes and a prognostic signature for predicting breast cancer prognosis and response to immunotherapy.

Background: Breast cancer (BRCA) remains by far the most life-threatening malignancy in women. Resistance to BRCA treatment may be counteracted by the induction of ferroptosis in combination with immunotherapy. The study aims develop iron death-related prognostic models to predict prognosis and immunotherapy effects in BRCA patients. Methods: We collected and organized 22 ferroptosis-related pathways and quantified their pathway activities using single-sample gene set enrichment analysis (ssGSEA). Coenzyme Q10 (CoQ10) is a pathway associated with prognosis in patients with BRCA. We compared the differences between patients with different CoQ10 expressions in terms of prognosis, biological function, mutational profile, immune infiltration, immunotherapy, and chemotherapeutic drug sensitivity. Results: Patients with high CoQ pathway activity had a worse prognosis. In addition, patients with high CoQ activity showed greater cell cycle activation and lower immune infiltration. Based on different CoQ10 expression patterns, we developed a CoQ10-related prognostic model. The accuracy and stability of CoQ10-related prognostic models were well validated in the training set and multiple validation sets. High-risk patients showed a propensity for immune depletion and tolerance to immunotherapy. There were also some differences in the sensitivity to different chemotherapeutic agents between high- and low-risk patients. Conclusions: We have constructed and validated a CoQ10-related gene model that can predict the prognosis of BRCA. Critically, it may serve as a reference standard to guide outcome prognostication in patients with BRCA.