Phospholipids as cancer biomarkers: Mass spectrometry‐based analysis

Abstract

Lipids, particularly phospholipids (PLs), are key components of cellular membrane. PLs play important and diverse roles in cells such as chemical-energy storage, cellular signaling, cell membranes, and cell-cell interactions in tissues. All these cellular processes are pertinent to cells that undergo transformation, cancer progression, and metastasis. Thus, there is a strong possibility that some classes of PLs are expected to present in cancer cells and tissues in cellular physiology. The mass spectrometric soft-ionization techniques, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization (MALDI) are well-established in the proteomics field, have been used for lipidomic analysis in cancer research. This review focused on the applications of mass spectrometry (MS) mainly on ESI-MS and MALDI-MS in the structural characterization, molecular composition and key roles of various PLs present in cancer cells, tissues, blood, and urine, and on their importance for cancer-related problems as well as challenges for development of novel PL-based biomarkers. The profiling of PLs helps to rationalize their functions in biological systems, and will also provide diagnostic information to elucidate mechanisms behind the control of cancer, diabetes, and neurodegenerative diseases. The investigation of cellular PLs with MS methods suggests new insights on various cancer diseases and clinical applications in the drug discovery and development of biomarkers for various PL-related different cancer diseases. PL profiling in tissues, cells and body fluids also reflect the general condition of the whole organism and can indicate the existence of cancer and other diseases. PL profiling with MS opens new prospects to assess alterations of PLs in cancer, screening specific biomarkers and provide a basis for the development of novel therapeutic strategies. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:107-138, 2018.

Differential diagnosis of human lung tumors using surface desorption atmospheric pressure chemical ionization imaging mass spectrometry

“…[42][43][44][45][46]55,56 A signi-cant increase in multiple phosphatidylcholines (PCs) and a decrease in several specic sphingomyelins (SMs) were observed from tumor to adjacent normal tissue particularly, enhanced levels of choline (C 5 in the MALDI-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS), the potassium or sodium adducts form mechanism of which is the same as the result of this study. 46,58 Different formations of these ions produced are contributed to the different main ionization mechanisms of ESI and DAPCI, which are complementary for compounds identi-cation and potential biomarkers discovery.…”

“…[40][41][42][43][44] Lipid distributions in cancerous tissues have demonstrated to vary in composition from adjacent normal tissue. [40][41][42][43] Alterations in the phospholipids composition of tissues have been reported to a key signature for various certain cancer 45,46 and Alzheimer's diseases. 47 Determination of the spatial distribution of particular lipids in tissue sections has been demonstrated to be very important in tumor diagnosis and surgical resection.…”

Structure Annotation and Quantification of Wheat Seed Oxidized Lipids by High-Resolution LC-MS/MS

“…The MS/MS fragmentation patterns of glycerides, PLs and GLs, have been analyzed extensively regarding acyl and head group composition (Byrdwell and Neff, 2002;Taguchi et al, 2005;Schwudke et al, 2006;Manicke et al, 2008;Ivanova et al, 2009;Murphy and Axelsen, 2011;Anesi and Guella, 2015;Bandu et al, 2016;Maciel et al, 2016), but the utilization of highresolution MS/MS spectra for the identification and structural annotation of oxidized lipids was hitherto far less investigated (Vu et al, 2012). We found a high generalizability between nominal mass MS/MS spectra of authentic standards available at LIPID MAPS (www.…”

“…PLs were regarded as MS/MS validated when we detected a fragment or NL specific for the corresponding head group (Bandu et al, 2016) in combination with the predicted adduct or in protonated form. We scanned for intact and oxidized PC, PE, PG, PI, and their lysoforms, but only for PC, lysoPC, and PE were oxidized lipids MS/MS validated (Table IV).…”

Personalized Proteomics: The Future of Precision Medicine

“…Multiplexing the analysis of a patient sample could significantly reduce the time required for a patient’s diagnosis. Several biomarkers detectable by mass spectrometry have already been associated with cardiac events (trimethylamine-N-oxide, MMP-2 MMP-9, MMP10, NGAL) [87–92], intestinal bowel disease [83], and numerous targets for various cancers [84–86,93–97]. …”