Serum Oxidized Phospholipids Are Increased in Pancreatic Cancer

Abstract

Purpose: There is an enormous spectrum of circulating bioactive lipid molecules that can be quantified using sensitive mass spectrometry techniques. Discovering differential patterns in the plasma “lipidome” may elucidate oxidation-mediated injury and enzymatic pathways involved in disease states such as cancer. In this study, we used a novel liquid chromatography dual mass spectrometry (LC-MS/MS) lipid array to quantify a family of oxidized products of phosphotidylcholine (Ox-PC). We sought to determine whether differences in serum phospholipid content exist between patients with pancreatic cancer (PC), chronic pancreatitis (CP), and disease-free controls. Methods: An IRB-approved prospective, cross-over study was conducted. Adult patients with biopsy-proven PC, established CP, and disease-free controls consented to undergo a blood draw. Serum aliquots were stored with antioxidant cocktail and argon overlay to prevent artificial oxidation. Serum was analyzed for eight different products of phosphotidylcholine oxidation (OxPCs) using LC-MS/MS. The levels of the OxPCs were expressed as a ratio to their precursors PLPC and PAPC (different “species” of phosphotidylcholine comprised of linoleic and arachidonic acid, respectively). The Kruskal Wallis test was used to assess differences between groups. Results: The ratios of several OxPCs to their precursors were significantly increased in PC compared to controls and CP [Table]. Some OxPCs appeared useful for ruling out PC if an appropriate cutpoint was chosen. The ON-PC: PLPC ratio demonstrated the best discrimination. An ON-PC:PLPC ratio >8 had 100% sensitivity for detecting cancer, and helped “rule out” pancreatic cancer in 41 of 67 patients without cancer (61% specificity).Table: OxPC productsConclusion: Circulating oxidized phospholipids are increased in patients with pancreatic cancer compared to patients with chronic pancreatitis and diseasefree controls. Measurement of certain serum OxPCs may serve as a useful initial screening test for pancreatic cancer.Figure: Differential expression of the OxPC product, ON-PC. The overall Kruskal Wallis p value is 0.006. Dunn's multiple comparisons test showed significantly higher values for PC compared with controls and CP.