Construction and Analysis of a Mitochondrial Metabolism-Related Prognostic Model for Breast Cancer to Evaluate Survival and Immunotherapy

• Published in: The Journal of membrane biology 2024-04, Vol.257 (1-2), p.63-78
• Main Authors: Lin, Yuting, Huang, Zhongxin, Zhang, Baogen, Yang, Hanhui, Yang, Shu
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Drug development; Female; Gene expression; Gene set enrichment analysis; Genetic Risk Score; Human Physiology; Humans; Immunosuppressive agents; Immunotherapy; Irinotecan; Life Sciences; Malignancy; Medical prognosis; Metabolism; Mitochondria; Multivariate analysis; Nomograms; Oxaliplatin; Prognosis; Regression analysis; Risk; Survival; Targeted cancer therapy; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/s00232-024-00308-1

As one of the most prevalent malignancies among women, breast cancer (BC) is tightly linked to metabolic dysfunction. However, the correlation between mitochondrial metabolism-related genes (MMRGs) and BC remains unclear. The training and validation datasets for BC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. MMRG-related data were obtained from the Molecular Signatures Database. A risk score prognostic model incorporating MMRGs was established based on univariate, LASSO, and multivariate Cox regression analyses. Independent factors affecting BC prognosis were identified through regression analysis and presented in a nomogram. Single-sample gene set enrichment analysis was employed to assess the immune levels of high-risk (HR) and low-risk (LR) groups. The sensitivity of BC patients in the two groups to common anti-tumor drugs was evaluated by utilizing the Genomics of Drug Sensitivity in Cancer database. 12 MMRGs significantly associated with survival were selected from 1234 MMRGs. A 12-gene risk score prognostic model was built. In the multivariate regression analysis incorporating classical clinical factors, the MMRG-related risk score remained an independent prognostic factor. As revealed by tumor immune microenvironment analysis, the LR group with higher survival rates had elevated immune levels. The drug sensitivity results unmasked that the LR group demonstrated higher sensitivity to Irinotecan, Nilotinib, and Oxaliplatin, while the HR group demonstrated higher sensitivity to Lapatinib. The development of MMRG characteristics provides a comprehensive understanding of mitochondrial metabolism in BC, aiding in the prediction of prognosis and tumor microenvironment, and offering promising therapeutic choices for BC patients with different MMRG risk scores. Graphical abstract