The reprogramming of lipid metabolism is a hallmark of many
cancers that has been shown to promote
breast cancer progression. While several
lipid signatures associated with
breast cancer aggressiveness have been identified, a comprehensive lipidomic analysis specifically targeting the triple-negative subtype of
breast cancer (TNBC) may be required to identify novel
biomarkers and therapeutic targets for this most aggressive subtype of
breast cancer that still lacks effective
therapies. In this current study, our global LC-MS-based lipidomics platform was able to measure 684 named
lipids across 15
lipid classes in 70 TNBC
tumors. Multivariate survival analysis found that higher levels of
sphingomyelins were significantly associated with better disease-free survival in TNBC patients. Furthermore, analysis of publicly available gene expression datasets identified that decreased production of
ceramides and increased accumulation of sphingoid base intermediates by metabolic
enzymes were associated with better survival outcomes in TNBC patients. Our LC-MS lipidomics profiling of TNBC
tumors has, for the first time, identified
sphingomyelins as a potential prognostic marker and implicated
enzymes involved in
sphingolipid metabolism as candidate therapeutic targets that warrant further investigation.