Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Investigating the Potential of Lipids for Use as Biomarkers for Glioblastoma via an Untargeted Lipidomics Approach

  • Burcak Soylemez (Department of Neurosurgery, Sivas Cumhuriyet University Hospital) ;
  • Zekeriya Bulut (Department of Neurosurgery, Sivas Cumhuriyet University Hospital) ;
  • Serap Sahin-Bolukbasi (Department of Biochemistry, Faculty of Pharmacy, Afyonkarahisar Health Sciences University)
  • Received : 2022.04.27
  • Accepted : 2022.07.28
  • Published : 2023.03.01
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Abstract

Objective : The types and functions of lipids involved in glioblastoma (GB) are not well known. Lipidomics is a new field that examines cellular lipids on a large scale and novel aplication of lipidomics in the biomedical sciences have emerged. This study aimed to investigate the potential of blood lipids for use as biomarkers for the diagnosis of GB via untargated lipidomic approach. Gaining a deeper understanding of lipid metabolism in patients with GB can contribute to the early diagnosis with GB patiens and also development of novel and better therapeutic options. Methods : This study was performed using blood samples collected from 14 patients (eight females and six males) and 14 controls (eight females and six males). Lipids were extracted from blood samples and quantified using phosphorus assay. Lipid profiles of between patients with GB and controls were compared via an untargeted lipidomics approach using 6530 Accurate-Mass Q-TOF LC/MS mass spectrometer. Results : According to the results obtained using the untargeted lipidomics approach, differentially regulated lipid species, including fatty acid (FA), glycerolipid (GL), glycerophospholipid (PG), saccharolipid (SL), sphingolipid (SP), and sterol lipid (ST) were identified between in patients with GB and controls. Conclusion : Differentially regulated lipids were identified in patients with GB, and these lipid species were predicted as potential biomarkers for diagnosis of GB.

Keywords

References

  1. Astarita G, Piomelli D : Towards a whole-body systems [multi-organ] lipidomics in Alzheimer's disease. Prostaglandins Leukot Essent Fatty Acids 85 : 197-203, 2011 https://doi.org/10.1016/j.plefa.2011.04.021
  2. Bartlett GR : Phosphorus assay in column chromatography. J Biol Chem 234 : 466-468, 1959 https://doi.org/10.1016/S0021-9258(18)70226-3
  3. Beloribi-Djefaflia S, Vasseur S, Guillaumond F : Lipid metabolic reprogramming in cancer cells. Oncogenesis 5 : e189, 2016
  4. Bilgin E, Duman BB, Altintas S, Cil T, Gezercan Y, Okten AI : Predictors of survival in Turkish patients with primary glioblastoma. Turk Neurosurg 31 : 641-653, 2021 https://doi.org/10.5137/1019-5149.JTN.33332-20.3
  5. Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J : Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 39 : 1594-1600, 1998 https://doi.org/10.1016/S0022-2275(20)32188-X
  6. Bligh EG, Dyer WJ : A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37 : 911-917, 1959 https://doi.org/10.1139/y59-099
  7. Bretillon L, Siden A, Wahlund LO, Lutjohann D, Minthon L, Crisby M, et al. : Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci Lett 293 : 87-90, 2000 https://doi.org/10.1016/S0304-3940(00)01466-X
  8. Del Boccio P, Pieragostino D, Di Ioia M, Petrucci F, Lugaresi A, De Luca G, et al. : Lipidomic investigations for the characterization of circulating serum lipids in multiple sclerosis. J Proteomics 74 : 2826-2836, 2011 https://doi.org/10.1016/j.jprot.2011.06.023
  9. Ejsing CS, Sampaio JL, Surendranath V, Duchoslav E, Ekroos K, Klemm RW, et al. : Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc Natl Acad Sci U S A 106 : 2136-2141, 2009 https://doi.org/10.1073/pnas.0811700106
  10. Guerrera IC, Astarita G, Jais JP, Sands D, Nowakowska A, Colas J, et al. : A novel lipidomic strategy reveals plasma phospholipid signatures associated with respiratory disease severity in cystic fibrosis patients. PLoS One 4 : e7735, 2009
  11. Guo D, Bell EH, Chakravarti A : Lipid metabolism emerges as a promising target for malignant glioma therapy. CNS Oncol 2 : 289-299, 2013 https://doi.org/10.2217/cns.13.20
  12. Ha SJ, Showalter G, Cai S, Wang H, Liu WM, Cohen-Gadol AA, et al. : Lipidomic analysis of glioblastoma multiforme using mass spectrometry. Anal Chem 79 : 8423-8430, 2007 https://doi.org/10.1021/ac071413m
  13. Han X : Multi-dimensional mass spectrometry-based shotgun lipidomics and the altered lipids at the mild cognitive impairment stage of Alzheimer's disease. Biochim Biophys Acta 1801 : 774-783,
  14. Holdhoff M, Yovino SG, Boadu O, Grossman SA : Blood-based biomarkers for malignant gliomas. J Neurooncol 113 : 345-352, 2013 https://doi.org/10.1007/s11060-013-1144-0
  15. Hu X, Matsumoto K, Jung RS, Weston TA, Heizer PJ, He C, et al. : GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. Elife 8 : e47178, 2019
  16. Jayaram S, Gupta MK, Polisetty RV, Cho WC, Sirdeshmukh R : Towards developing biomarkers for glioblastoma multiforme: a proteomics view. Expert Rev Proteomics 11 : 621-639, 2014 https://doi.org/10.1586/14789450.2014.939634
  17. Jia L, Wang C, Zhao S, Lu X, Xu G : Metabolomic identification of potential phospholipid biomarkers for chronic glomerulonephritis by using high performance liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 860 : 134-140, 2007 https://doi.org/10.1016/j.jchromb.2007.10.033
  18. Kinsey GR, Blum JL, Covington MD, Cummings BS, McHowat J, Schnellmann RG : Decreased iPLA2gamma expression induces lipid peroxidation and cell death and sensitizes cells to oxidant-induced apoptosis. J Lipid Res 49 : 1477-1487, 2008 https://doi.org/10.1194/jlr.M800030-JLR200
  19. Kuemmerle NB, Rysman E, Lombardo PS, Flanagan AJ, Lipe BC, Wells WA, et al. : Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther 10 : 427-436, 2011 https://doi.org/10.1158/1535-7163.MCT-10-0802
  20. LIPID MAPS®  : LIPID gateway, lipidomics. Available at : http://www.lipidmaps.org/
  21. MetaboAnalyst : MetaboAnalyst - statistical, functional and integrative analysis of metabolomics data. Available at : https://www.metaboanalyst.ca/
  22. Min HK, Lim S, Chung BC, Moon MH : Shotgun lipidomics for candidate biomarkers of urinary phospholipids in prostate cancer. Anal Bioanal Chem 399 : 823-830, 2011 https://doi.org/10.1007/s00216-010-4290-7
  23. Muro E, Atilla-Gokcumen GE, Eggert US : Lipids in cell biology: how can we understand them better? Mol Biol Cell 25 : 1819-1823, 2014 https://doi.org/10.1091/mbc.e13-09-0516
  24. Navas-Iglesias N, Carrasco-Pancorbo A, Cuadros-Rodriguez L : From lipids analysis towards lipidomics, a new challenge for the analytical chemistry of the 21st century. Part II: analytical lipidomics. Trends Anal Chem 28 : 393-403, 2009
  25. Ollero M, Astarita G, Guerrera IC, Sermet-Gaudelus I, Trudel S, Piomelli D, et al. : Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients. J Lipid Res 52 : 1011-1022, 2011 https://doi.org/10.1194/jlr.P013722
  26. Peterson B, Stovall K, Monian P, Franklin JL, Cummings BS : Alterations in phospholipid and fatty acid lipid profiles in primary neocortical cells during oxidant-induced cell injury. Chem Biol Interact 174 : 163-176, 2008 https://doi.org/10.1016/j.cbi.2008.05.028
  27. Pinto RC, Trygg J, Gottfries J : Advantages of orthogonal inspection in chemometrics. J Chemom 26 : 231-235, 2012 https://doi.org/10.1002/cem.2441
  28. Sabbagh MN, Sandhu S, Kolody H, Lahti T, Silverberg NB, Sparks DL : Studies on the effect of the apolipoprotein E genotype on the lipid profile in Alzheimer's disease. Curr Alzheimer Res 3 : 157-160, 2006 https://doi.org/10.2174/156720506776383013
  29. Santos CR, Schulze A : Lipid metabolism in cancer. FEBS J 279 : 2610-2623, 2012 https://doi.org/10.1111/j.1742-4658.2012.08644.x
  30. Schwarz E, Prabakaran S, Whitfield P, Major H, Leweke FM, Koethe D, et al. : High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides. J Proteome Res 7 : 4266-4277, 2008 https://doi.org/10.1021/pr800188y
  31. Shukla G, Alexander GS, Bakas S, Nikam R, Talekar K, Palmer JD, et al. : Advanced magnetic resonance imaging in glioblastoma: a review. Chin Clin Oncol 6 : 40, 2017
  32. Taguchi R, Hayakawa J, Takeuchi Y, Ishida M : Two-dimensional analysis of phospholipids by capillary liquid chromatography/electrospray ionization mass spectrometry. J Mass Spectrom 35 : 953-966, 2000 https://doi.org/10.1002/1096-9888(200008)35:8<953::AID-JMS23>3.0.CO;2-4
  33. Taib B, Aboussalah AM, Moniruzzaman M, Chen S, Haughey NJ, Kim SF, et al. : Lipid accumulation and oxidation in glioblastoma multiforme. Sci Rep 9 : 19593, 2019
  34. Touboul D, Gaudin M : Lipidomics of Alzheimer's disease. Bioanalysis 6 : 541-561, 2014 https://doi.org/10.4155/bio.13.346
  35. Tugnoli V, Tosi MR, Tinti A, Trinchero A, Bottura G, Fini G : Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy. Biopolymers 62 : 297-306, 2001 https://doi.org/10.1002/bip.10005
  36. Vaz FM, Pras-Raves M, Bootsma AH, van Kampen AH : Principles and practice of lipidomics. J Inherit Metab Dis 38 : 41-52, 2015 https://doi.org/10.1007/s10545-014-9792-6
  37. Wood PL : Mass spectrometry strategies for clinical metabolomics and lipidomics in psychiatry, neurology, and neuro-oncology. Neuropsychopharmacology 39 : 24-33, 2014 https://doi.org/10.1038/npp.2013.167
  38. Yang K, Rich JN : A delicate initiation: lipolysis of lipid droplets fuels glioblastoma. Mol Cell 81 : 2686-2687, 2021 https://doi.org/10.1016/j.molcel.2021.06.013
  39. Zhang L, Peterson BL, Cummings BS : The effect of inhibition of Ca2+- independent phospholipase A2 on chemotherapeutic-induced death and phospholipid profiles in renal cells. Biochem Pharmacol 70 : 1697-1706, 2005 https://doi.org/10.1016/j.bcp.2005.09.008
  40. Zhang RD, Price JE, Fujimaki T, Bucana CD, Fidler IJ : Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. Am J Pathol 141 : 1115-1124, 1992
  41. Zhang Y, Wang Y, Guo S, Guo Y, Liu H, Li Z : Ammonia-treated N-(1-naphthyl) ethylenediamine dihydrochloride as a novel matrix for rapid quantitative and qualitative determination of serum free fatty acids by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry. Anal Chim Acta 794 : 82-89, 2013 https://doi.org/10.1016/j.aca.2013.07.060
  42. Zhao YY, Cheng XL, Lin RC : Lipidomics applications for discovering biomarkers of diseases in clinical chemistry. Int Rev Cell Mol Biol 313 : 1-26, 2014 https://doi.org/10.1016/B978-0-12-800177-6.00001-3
  43. Zhou X, Mao J, Ai J, Deng Y, Roth MR, Pound C, et al. : Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics. PLoS One 7 : e48889, 2012
  44. Zhou X, Mao J, He Z, Henegar J : Lipidomics in identifying lipid biomarkers of prostate cancer. FASEB J 24(S1) : 354.6, 2010