BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (CRPC) is not fully understood. While it is known that increases in select lipids correlates to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments are well characterized.MethodsWe addressed this gap-in-knowledge using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell

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... ines combined with quantitative LC-ESI-Orbitrap-MS lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment (LIPEA).ResultsThis approach identified several lipid regulatory pathways associated with Docetaxel resistance in PCa. These included those controlling glycerophospholipid metabolism, sphingolipid signaling pathways and ferroptosis. In total, 7,460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) and had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). These cells also had higher levels of ceramides release into the media.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of prostate cancer.