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Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival

1
Alkek Center for Molecular Discovery and Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
2
Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
3
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA
4
Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Metabolites 2018, 8(3), 41; https://doi.org/10.3390/metabo8030041
Received: 1 May 2018 / Revised: 2 July 2018 / Accepted: 4 July 2018 / Published: 13 July 2018
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. View Full-Text
Keywords: lipidomics; sphingomyelin; sphingolipid; triple-negative breast cancer lipidomics; sphingomyelin; sphingolipid; triple-negative breast cancer
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Purwaha, P.; Gu, F.; Piyarathna, D.W.B.; Rajendiran, T.; Ravindran, A.; Omilian, A.R.; Jiralerspong, S.; Das, G.; Morrison, C.; Ambrosone, C.; Coarfa, C.; Putluri, N.; Sreekumar, A. Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival. Metabolites 2018, 8, 41.

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