Elevated levels of hydroxylated phosphocholine lipids in the blood serum of breast cancer patients

Abstract

The difference in serum phospholipid content between stage-IV breast cancer patients and disease-free individuals was studied by employing a combination of chemometric statistical analysis tools and mass spectrometry. Chloroform-extracted serum samples were profiled for their lipid class composition and structure using precursor ion, neutral loss, and product ion tandem mass spectrometric (MS/MS) scanning experiments. Changes in the relative abundance of phospholipids in serum as a consequence of cancer progression, measured through electrospray ionization (ESI) mass spectrometry of flow-injected serum samples collected from 25 disease-free individuals and 50 patients diagnosed with stage-IV breast cancer, were statistically evaluated using principal component analysis (PCA), analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis. Lipids whose abundance changed significantly as a consequence of cancer progression were structurally characterized using product ion spectra, and independently quantified using precursor ion scan experiments against an internal standard of known concentration. Phosphocholine lipids that displayed a statistically significant change as a consequence of cancer progression were found to contain an oxidized fatty acid moiety as determined by MS3 experiments.

Structural motifs in primary oxidation products of palmitoyl‐arachidonoyl‐phosphatidylcholines by LC‐MS/MS

“…Oxidized phospholipids (OxPL) are increasingly becoming the focus of the scientific community largely due to the emerging roles of OxPL in the onset and development of inflammatory and infection, [3][4][5][6] and as potential biomarkers in disease diagnostics. [40] Much of the work done on the role of OxPL [11,14,16,[18][19][20][21]24,25] together with the identification of oxidized phosphatidylcholine (OxPC) lipids in minimally oxidized low density lipoproteins (oxLDL) and their accumulation in circulation [9,17,37,38,40] and atherosclerotic lesions [48,49] contributed to the notion that OxPC are key players in regulating endothelial dysfunction and the pathogenesis of atherosclerosis. [3][4][5] The pro-and anti-inflammatory roles described for OxPC are thought to be regulated in a concentration-dependent manner, [16] though because many of the works published use whole extracts of OxPAPC to carry out their studies, the structural/ biological activity relationships remain poorly understood.…”

Phospholipids as cancer biomarkers: Mass spectrometry‐based analysis

“…The analysis of PLs in cancer cells, tissues, and biofluids is a novel approach and displays growing interest to develop candidate biomarkers of various cancers. Alterations in PL profiles have been associated with cancer diagnosis and treatment (Wenk, 2005;Hammad et al, 2009;Thomas et al, 2010) and specific lipids might be involved in the onset and evolution of cancer (Xiao et al, 2000;Oremek, Sapoutzis, & Lorenz, 2002;Sutphen et al, 2004;Shimma et al, 2007;Dill et al, 2009Dill et al, , 2010Dill et al, , 2011Kim et al, 2009Kim et al, , 2013Min, Kong, & Moon, 2010Jeong et al, 2011;Kang et al, 2011;Liu, Cooks, & Ouyang, 2011Park et al, 2011;Patterson et al, 2011;Doria et al, 2012;Guo et al, 2012;Ishikawa et al, 2012;Lee et al, 2012;Ide et al, 2013;Kurabe et al, 2013;Liao et al, 2013;Xu et al, 2013;Jones et al, 2014;Mirnezami et al, 2014;Patel et al, 2014). Biomarker detection and evaluation based on MS methods is so far well-established in cancer proteomics, but it also has a potential importance in cancer lipidomics.…”

Formation and Regulation of Mitochondrial Membranes

“…Mitochondrial CL peroxidation appears to be an early event preceding the intrinsic apoptotic cell death [11]. Because its role in apoptosis and mitochondrial function, CL levels and CL peroxidation have been implicated in several human diseases such as atherosclerosis [12], cancer [13], Barth syndrome [14], and neurodegenerative disorders including Alzheimer's [15] and Parkinson's disease [16]. …”