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Elevated levels of hydroxylated phosphocholine lipids in the blood serum of breast cancer patients
Authors:Loubna A Hammad  Guangxiang Wu  Marwa M Saleh  Iveta Klouckova  Lacey E Dobrolecki  Robert J Hickey  Lauren Schnaper  Milos V Novotny  Yehia Mechref
Institution:1. METACyt Biochemical Analysis Center, Department of Chemistry, Indiana University, Bloomington, Indiana 47405;2. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202;3. Indiana University Cancer Center, Indianapolis, Indiana 46202;4. Breast Cancer Center, Greater Baltimore Medical Center, Baltimore, MD 21204
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. Copyright © 2009 John Wiley & Sons, Ltd.
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