Liquid Chromatography Mass Spectrometry for Quantifying Plasma Lysophospholipids: Potential Biomarkers for Cancer Diagnosis

Mandi Murph, Tamotsu Tanaka, Jihai Pang, Edward Felix, Shuying Liu, Rosanne Trost, Andrew K. Godwin, Robert Newman, Gordon Mills

    Research output: Chapter in Book/Report/Conference proceedingChapter

    82 Scopus citations


    Cancer is a complex disease with many genetic and epigenetic aberrations that result in development of tumorigenic phenotypes. While many factors contribute to the etiology of cancer, emerging data implicate lysophospholipids acting through specific cell-surface, and potentially intracellular, receptors in acquiring the transformed phenotype propagated during disease. Lysophospholipids bind to and activate specific cell-surface G protein-coupled receptors (GPCRs) that initiate cell growth, proliferation, and survival pathways, and show altered expression in cancer cells. In addition, a number of enzymes that increase lysophospholipid production are elevated in particular cell lineages and cancer patients' cells, whereas in a subset of patients, the enzymes degrading lysophospholipids are decreased. Thus, ideal conditions are established to increase lysophospholipids in the tumor microenvironment. Indeed, ascites from ovarian cancer patients, which reflects both the tumor environment and a tumor-conditioned media, exhibits markedly elevated levels of specific lysophospholipids as well as one of the enzymes involved in production of lysophospholipids: autotaxin (ATX). The potential sources of lysophospholipids in the tumor microenvironment include tumor cells and stroma, such as mesothelial cells, as well as inflammatory cells and platelets activated by the proinflammatory tumor environment. If lysophospholipids diffuse from the tumor microenvironment into the bloodstream and persist, they have the potential to serve as early diagnostic markers as well as potential monitors of tumor response to therapy. Many scientific and technical challenges need to be resolved to determine whether lysophospholipids or the enzymes producing lysophospholipids alone or in combination with other markers have the potential to contribute to early diagnosis. Breast cancer is the most frequently diagnosed cancer among women. Mammography is associated with morbidity and has a high false positive and false negative rate. Thus, there is a critical need for biomarkers that can contribute to reduced false positive and false negative diagnoses, and to identify, stage, and/or predict prognosis of this disease to improve patient management. Here we describe a technical approach that can be applied to human blood plasma to measure the concentration of growth factor-like lysophospholipids contained in circulation. Using liquid chromatography mass spectrometry (LC/MS/MS), we quantified the amount of lysophosphatidic acid (16:0, 18:0, 18:1, 18:2, and 20:4), lysophosphatidylinositol (18:0), lysophosphatidylserine (18:1), lysophosphatidylcholine (16:0, 18:0, 18:1, 18:2, and 20:4), sphingosine-1-phosphate, and sphingosylphosphorylcholine species from human female plasma samples with malignant, benign, or no breast tumor present. Other methods described here include handling patient blood samples, lipid extraction, and factors that affect lysophospholipid production and loss during sample handling.

    Original languageEnglish (US)
    Title of host publicationLipidomics and Bioactive Lipids
    Subtitle of host publicationSpecialized Analytical Methods and Lipids in Disease
    EditorsAlex Brown
    Number of pages25
    StatePublished - Dec 1 2007

    Publication series

    NameMethods in Enzymology
    ISSN (Print)0076-6879

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology

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    Murph, M., Tanaka, T., Pang, J., Felix, E., Liu, S., Trost, R., Godwin, A. K., Newman, R., & Mills, G. (2007). Liquid Chromatography Mass Spectrometry for Quantifying Plasma Lysophospholipids: Potential Biomarkers for Cancer Diagnosis. In A. Brown (Ed.), Lipidomics and Bioactive Lipids: Specialized Analytical Methods and Lipids in Disease (pp. 1-25). (Methods in Enzymology; Vol. 433).