The Metabolomic Characteristics and Dysregulation of Fatty Acid Esters of Hydroxy Fatty Acids in Breast Cancer

Lipid reprogramming metabolism is crucial for supporting tumor growth in breast cancer and investigating potential tumor biomarkers. Fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of endogenous lipid metabolites with anti-diabetic and anti-inflammatory properties that have been discovered in recent years. Our previous targeted analysis of sera from breast cancer patients revealed a significant down-regulation of several FAHFAs. In this study, we aimed to further explore the relationship between FAHFAs and breast cancer by employing chemical isotope labeling combined with liquid chromatography-mass spectrometry (CIL-LC-MS) for profiling of FAHFAs in tumors and adjacent normal tissues from breast cancer patients. Statistical analysis identified 13 altered isomers in breast cancer. These isomers showed the potential to distinguish breast cancer tissues with an area under the curve (AUC) value above 0.9 in a multivariate receiver operating curve model. Furthermore, the observation of up-regulated 9-oleic acid ester of hydroxy stearic acid (9-OAHSA) and down-regulated 9-hydroxystearic acid (9-HSA) in tumors suggests that breast cancer shares similarities with colorectal cancer, and their potential mechanism is to attenuate the effects of pro-apoptotic 9-HSA by enhancing the synthesis of FAHFAs, thereby promoting tumor survival and progression through this buffering system.

Automated summary

Lipid reprogramming metabolism plays a crucial role in breast cancer growth and potential biomarkers. Fatty acid esters of hydroxy fatty acids (FAHFAs), a class of endogenous lipid metabolites, have been found to have anti-diabetic and anti-inflammatory properties. In this study, the researchers aimed to explore the relationship between FAHFAs and breast cancer by analyzing FAHFAs in tumors and adjacent normal tissues using chemical isotope labeling combined with liquid chromatography-mass spectrometry (CIL-LC-MS). Statistical analysis identified 13 altered isomers in breast cancer, which showed potential in distinguishing breast cancer tissues. Furthermore, the up-regulation of 9-oleic acid ester of hydroxy stearic acid (9-OAHSA) and down-regulation of 9-hydroxystearic acid (9-HSA) in tumors suggest that breast cancer shares similarities with colorectal cancer in terms of attenuating pro-apoptotic effects and promoting tumor survival and progression through FAHFA synthesis.