Discovery of a New Mitophagy-related Gene Signature for Predicting the Outlook and Immunotherapy in Triple-negative Breast Cancer

Mitophagy is an essential cellular process that is conserved and crucial for maintaining cellular balance by selectively eliminating malfunctioning mitochondria. However, there is still limited knowledge regarding the influence of mitophagy-related genes (MRGs) on the prognosis and response to treatment of triple-negative breast cancer (TNBC). In here, the TCGA and GEO databases were used to acquire the transcriptomic and clinical information of patients with TNBC, correspondingly. Using LASSO and multivariable Cox regression analyses, a risk signature related to mitophagy was established based on the prognostic MRGs. The prognostic signature associated with mitophagy consisted of five genes (BSG, JMJD6, DNAJA3, DISC1, and SQSTM1) and independently predicted the prognosis of patients with TNBC, regardless of clinical factors (p < 0.05). Patients classified within the high-risk group demonstrated significantly lower overall survival rates when contrasted with those in the low-risk group. The model exhibited excellent performance in predicting survival and risk stratification, as evidenced by the receiver operating characteristic and C-index. The findings stayed unchanged following external validation. Moreover, we observed a notable variation in the tumor immune microenvironment among the different risk categories. Patients with a low risk of TNBC demonstrated a more favorable response to immunotherapy compared to patients with a high risk. In conclusion, our study uncovered the possible impacts of MRGs on the tumor microenvironment, clinical and pathological characteristics, and outlook of TNBC. The CRG-related signature was strongly linked to the immune response against TNBC and has the potential to serve as a valuable tool in predicting the prognosis and immunotherapy response of patients.