The lipid metabolome of clear cell renal cell carcinoma (CCRCC).
10609 Background: The commonest type of kidney cancer is CCRCC. Treatment approaches mostly target aberrant vasculature. However, kidney cancer is also known to accumulate lipids and a detailed knowledge of the lipid species present in these tumors could lead to a better understanding of the underlying aberrant metabolic pathways and suggest possible treatment strategies. Lipidomics is an emerging field driven by rapid advances in mass spectrometry (MS), and is widely used to discover biomarkers. We attempt to identify the lipidomic profile of CCRCC using a liquid chromatography MS-based approach (LC-MS). Methods: We utilized 6 fresh frozen representative samples of CCRCC and matching non-tumor areas of kidney from nephrectomy samples. Lipids and other non-polar cellular constituents were extracted from both CCRCC and control tissues by methyl-t-butyl ether /methanol. LC-MS based lipid profiling was performed on a Waters Q-ToF Premier MS coupled with Ultra Performance LC. The peak detection and alignment across all chromatograms were performed using the XCMS software (v 1.14.1, Scripps Center for Metabolomics). Statistical comparisons of the intensities of aligned peaks were performed using the XCMS-built-in Welch's t-test. Results: The outcome of XCMS was converted to a table that contains fold change, p-value and mass to charge ratio (m/z) for each peak, its corresponding retention time, and the integrated peak intensities from all samples. 224 peaks out of 1419 differed between CCRCC and the control group, with p <0.05, calculated by XCMS. About an equal number of analytes increased or decreased in CCRCC compared with control samples. Preliminary attempts to identify the analytes included use of METLIN (Scripps Center for Metabolomics) and HMDB (Human metabolome database, Genome Alberta & Genome Canada) databases. Many of the hits identified phosphatidylcholines, phosphatidylethanolamines, triacylglycerols and diacylglycerols, as well as other lipid species. Conclusions: The lipid metabolomic profile varied significantly between CCRCC and control. Further studies are required to confirm the identities of the lipid species contributing to this variation by obtaining structural information using tandem MS (LC-MS/MS).