Fatty acid metabolism has been deciphered to augment
tumorigenesis and
disease progression in addition to
therapy resistance via strengthened
lipid synthesis, storage, and catabolism.
Breast cancer is strongly associated with the
biological function of
fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that
tumor cells exhibit considerable plasticity based on
fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of
fatty acid metabolism in
breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable
fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The
Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of
Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on
Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of
tumor immune microenvironment, and the predictive significance in
therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of
fatty acid metabolism in
breast cancer, supporting novel insights into
breast cancer patients' prognosis and administrating effective
immunotherapy.