Phospholipids as Indicators of Docetaxel‐Resistant Castration‐Resistant Prostate Cancer
Abstract
The 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 plasma lipids correlates to decreased survival, neither the mechanisms mediating alterations in these lipids nor the correlation of resistance to treatment are well characterized. We addressed this gap‐in‐knowledge using in vitro models of non‐cancerous, hormone sensitive, CRPC and drug‐resistant cell lines combined with quantitative HPLC‐ESI‐Orbitrap‐MS lipidomic analysis. HPLC‐MS based metabolomic analysis identified 83 features that were significantly altered in the drug‐resistant cell lines as compared to non‐resistant control group. Within the 83 species, two were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer from previous studies. Principal component analysis (PCA) demonstrated that drug‐resistant and control cell‐lines were visually separated by these identified lipid biomarkers. Two out of the 83 lipid classes were identified as phosphatidylcholine (PC) 18:0/18:1 and PC 18:0/18:2), both of which had high level of abundance in Docetaxel‐resistant CRPC. An untargeted approach indicated that lipids corresponding to PC, phosphatidylglycerol (PG), phosphatidic acid (PA) and phosphatidylserine (PS) all had higher relative abundance in DR‐CRPC cells (DU145‐DR) compared to parent control (DU145). These data suggest that the lipidomic profiles of prostate cancer cells lines recapitulate lipidomic profiles in the plasma of prostate cancer patients. As such, these metastatic dependent and drug‐resistant cell lines may prove useful for understanding the molecular mechanisms mediating lipid changes in prostate cancer patients.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.675.1
Entities
People
- Brian S Cummings
- Lishann M. Ingram
- Maryam Mansoura
Organizations
- National Institute of Biomedical Imaging and Bioengineering
- United States Department of Defense
- University of Georgia