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Cancer Metabolism pp 275–297Cite as

Assessment of Metabolic Signature for Cancer Diagnosis Using Desorption Electrospray Ionization Mass Spectrometric Imaging

Part of the Methods in Molecular Biology book series (MIMB,volume 1928)

Abstract

Metabolic reprogramming is a hallmark of tumor development. A technique that can map this complex biochemical shift by taking a snapshot of various metabolites in a tissue specimen (biopsy) is of high utility in the context of cancer diagnosis. Desorption electrospray ionization mass spectrometric imaging (DESI-MSI) is such a powerful and emerging analytical technique to simultaneously visualize the distributions of hundreds of metabolites, lipids, and other small molecules in the biological tissue. In DESI-MSI, a fine spray of high-velocity charged microdroplets rapidly extracts molecular species from the tissue surface and subsequently transfers them to the mass spectrometer, while the sample is continuously moved in two dimensions under the impinging spray of microdroplets. This allows a detailed multiplex molecular mapping of the tissue. DESI-MSI enables simultaneous examination of hundreds of putative metabolic biomarkers, an approach that lends much more predictive power than simply evaluating one or a few candidate biomarkers. The speed, versatility, lack of complicated sample preparation, and operation at ambient conditions make DESI-MSI extremely promising as a rapid diagnostic and prognostic tool.

Key words

  • DESI-MSI
  • Tissue imaging
  • Cancer margin
  • Metabolites and lipids
  • Histopathology

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References

  1. Zhang J, Rector J, Lin JQ, Young JH, Sans M, Katta N, Giese N, Yu W, Nagi C, Suliburk J, Liu J, Bensussan A, DeHoog RJ, Garza KY, Ludolph B, Sorace AG, Syed A, Zahedivash A, Milner TE, Eberlin LS (2017) Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system. Sci Transl Med 9(406):eaan3968

    CrossRef  PubMed  PubMed Central  Google Scholar 

  2. Balog J, Sasi-Szabó L, Kinross J, Lewis MR, Muirhead LJ, Veselkov K, Mirnezami R, Dezső B, Damjanovich L, Darzi A, Nicholson JK, Takáts Z (2013) Intraoperative tissue identification using rapid evaporative ionization mass spectrometry. Sci Transl Med 5(194):194ra193–194ra193

    CrossRef  Google Scholar 

  3. Pirro V, Alfaro CM, Jarmusch AK, Hattab EM, Cohen-Gadol AA, Cooks RG (2017) Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry. Proc Natl Acad Sci U S A 114(26):6700–6705

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Hao J-J, Lin D-C, Dinh HQ, Mayakonda A, Jiang Y-Y, Chang C, Jiang Y, Lu C-C, Shi Z-Z, Xu X, Zhang Y, Cai Y, Wang J-W, Zhan Q-M, Wei W-Q, Berman BP, Wang M-R, Koeffler HP (2016) Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma. Nat Genet 48:1500

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  5. Axelson H, Fredlund E, Ovenberger M, Landberg G, Påhlman S (2005) Hypoxia-induced dedifferentiation of tumor cells—a mechanism behind heterogeneity and aggressiveness of solid tumors. Semin Cell Dev Biol 16(4):554–563

    CrossRef  CAS  PubMed  Google Scholar 

  6. Mazor T, Pankov A, Song JS, Costello JF (2016) Intratumoral heterogeneity of the epigenome. Cancer Cell 29(4):440–451

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  7. Levine AJ, Puzio-Kuter AM (2010) The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330(6009):1340–1344

    CrossRef  CAS  PubMed  Google Scholar 

  8. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029–1033

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  9. Iurlaro R, León-Annicchiarico CL, Muñoz-Pinedo C (2014) Chapter three - regulation of cancer metabolism by oncogenes and tumor suppressors. In: Galluzzi L, Kroemer G (eds) Methods in enzymology, vol 542. Academic Press, New York, pp 59–80. https://doi.org/10.1016/B978-0-12-416618-9.00003-0

    CrossRef  Google Scholar 

  10. Vermeersch KA, Styczynski MP (2013) Applications of metabolomics in cancer research. J Carcinog 12:9

    CrossRef  PubMed  PubMed Central  Google Scholar 

  11. DeBerardinis RJ, Chandel NS (2016) Fundamentals of cancer metabolism. Sci Adv 2(5):e1600200

    CrossRef  PubMed  PubMed Central  Google Scholar 

  12. Baenke F, Peck B, Miess H, Schulze A (2013) Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech 6(6):1353–1363

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  13. van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9(2):112–124

    CrossRef  PubMed  PubMed Central  Google Scholar 

  14. Andronesi OC, Rapalino O, Gerstner E, Chi A, Batchelor TT, Cahill DP, Sorensen AG, Rosen BR (2013) Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate. J Clin Invest 123(9):3659–3663

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  15. Leather T, Jenkinson MD, Das K, Poptani H (2017) Magnetic resonance spectroscopy for detection of 2-hydroxyglutarate as a biomarker for IDH mutation in gliomas. Metabolism 7(2):29

    CrossRef  Google Scholar 

  16. Kurhanewicz J, Vigneron DB (2008) Advances in MR spectroscopy of the prostate. Magn Reson Imaging Clin N Am 16(4):697–69x

    CrossRef  PubMed  PubMed Central  Google Scholar 

  17. Spratlin JL, Serkova NJ, Gail Eckhardt S (2009) Clinical applications of metabolomics in oncology: a review. Clin Cancer Res 15(2):431–440

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  18. Armitage EG, Southam AD (2016) Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics and lipidomics. Metabolomics 12(9):146

    CrossRef  PubMed  PubMed Central  Google Scholar 

  19. Ifa DR, Eberlin LS (2016) Ambient ionization mass spectrometry for cancer diagnosis and surgical margin evaluation. Clin Chem 62(1):111–123

    CrossRef  CAS  PubMed  Google Scholar 

  20. Takáts Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306(5695):471–473

    CrossRef  PubMed  Google Scholar 

  21. Wiseman JM, Ifa DR, Song Q, Cooks RG (2006) Tissue imaging at atmospheric pressure using desorption electrospray ionization (DESI) mass spectrometry. Angew Chem Int Ed 45(43):7188–7192

    CrossRef  CAS  Google Scholar 

  22. Eberlin LS, Norton I, Orringer D, Dunn IF, Liu X, Ide JL, Jarmusch AK, Ligon KL, Jolesz FA, Golby AJ, Santagata S, Agar NYR, Cooks RG (2013) Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors. Proc Natl Acad Sci U S A 110(5):1611–1616

    CrossRef  PubMed  PubMed Central  Google Scholar 

  23. Eberlin LS, Tibshirani RJ, Zhang J, Longacre TA, Berry GJ, Bingham DB, Norton JA, Zare RN, Poultsides GA (2014) Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging. Proc Natl Acad Sci U S A 111(7):2436–2441

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  24. Eberlin LS, Gabay M, Fan AC, Gouw AM, Tibshirani RJ, Felsher DW, Zare RN (2014) Alteration of the lipid profile in lymphomas induced by MYC overexpression. Proc Natl Acad Sci U S A 111(29):10450–10455

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  25. Eberlin LS (2014) DESI-MS imaging of lipids and metabolites from biological samples. In: Raftery D (ed) Mass spectrometry in metabolomics: methods and protocols. Springer New York, New York, NY, pp 299–311. https://doi.org/10.1007/978-1-4939-1258-2_20

    CrossRef  Google Scholar 

  26. Banerjee S, Mazumdar S (2012) Electrospray ionization mass spectrometry: a technique to access the information beyond the molecular weight of the analyte. Int J Analyt Chem 2012:282574

    Google Scholar 

  27. Fenn J, Mann M, Meng C, Wong S, Whitehouse C (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246(4926):64–71

    CrossRef  CAS  PubMed  Google Scholar 

  28. Kebarle P, Verkerk UH (2010) On the mechanism of electrospray ionization mass spectrometry (ESIMS). In: Electrospray and MALDI mass spectrometry. John Wiley & Sons, Inc., New York, pp 1–48. https://doi.org/10.1002/9780470588901.ch1

    CrossRef  Google Scholar 

  29. Perry RH, Bellovin DI, Shroff EH, Ismail AI, Zabuawala T, Felsher DW, Zare RN (2013) Characterization of MYC-induced tumorigenesis by in situ lipid profiling. Anal Chem 85(9):4259–4262

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  30. Eberlin LS, Margulis K, Planell-Mendez I, Zare RN, Tibshirani R, Longacre TA, Jalali M, Norton JA, Poultsides GA (2016) Pancreatic cancer surgical resection margins: molecular assessment by mass spectrometry imaging. PLoS Med 13(8):e1002108

    CrossRef  PubMed  PubMed Central  Google Scholar 

  31. Gouw AM, Eberlin LS, Margulis K, Sullivan DK, Toal GG, Tong L, Zare RN, Felsher DW (2017) Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma. Proc Natl Acad Sci U S A 114(17):4300–4305

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  32. Banerjee S, Zare RN, Tibshirani RJ, Kunder CA, Nolley R, Fan R, Brooks JD, Sonn GA (2017) Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids. Proc Natl Acad Sci U S A 114(13):3334–3339

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  33. Eberlin LS, Norton I, Dill AL, Golby AJ, Ligon KL, Santagata S, Cooks RG, Agar NYR (2012) Classifying human brain tumors by lipid imaging with mass spectrometry. Cancer Res 72(3):645–654

    CrossRef  CAS  PubMed  Google Scholar 

  34. Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cooks RG (2011) Desorption electrospray ionization mass spectrometry for lipid characterization and biological tissue imaging. Biochim Biophys Acta 1811(11):946–960

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang J, Feider CL, Nagi C, Yu W, Carter SA, Suliburk J, Cao HST, Eberlin LS (2017) Detection of metastatic breast and thyroid cancer in lymph nodes by desorption electrospray ionization mass spectrometry imaging. J Am Soc Mass Spectrom 28(6):1166–1174

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dória ML, McKenzie JS, Mroz A, Phelps DL, Speller A, Rosini F, Strittmatter N, Golf O, Veselkov K, Brown R, Ghaem-Maghami S, Takats Z (2016) Epithelial ovarian carcinoma diagnosis by desorption electrospray ionization mass spectrometry imaging. Sci Rep 6:39219

    CrossRef  PubMed  PubMed Central  Google Scholar 

  37. Abbassi-Ghadi N, Golf O, Kumar S, Antonowicz S, McKenzie JS, Huang J, Strittmatter N, Kudo H, Jones EA, Veselkov K, Goldin R, Takats Z, Hanna GB (2016) Imaging of esophageal lymph node metastases by desorption electrospray ionization mass spectrometry. Cancer Res 76(19):5647–5656

    CrossRef  CAS  PubMed  Google Scholar 

  38. Alfaro CM, Jarmusch AK, Pirro V, Kerian KS, Masterson TA, Cheng L, Cooks RG (2016) Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue. Anal Bioanal Chem 408(20):5407–5414

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  39. Calligaris D, Feldman DR, Norton I, Brastianos PK, Dunn IF, Santagata S, Agar NYR (2015) Molecular typing of Meningiomas by desorption electrospray ionization mass spectrometry imaging for surgical decision-making. Int J Mass Spectrom 377:690–698

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  40. Guenther S, Muirhead LJ, Speller AVM, Golf O, Strittmatter N, Ramakrishnan R, Goldin RD, Jones E, Veselkov K, Nicholson J, Darzi A, Takats Z (2015) Spatially resolved metabolic phenotyping of breast cancer by desorption electrospray ionization mass spectrometry. Cancer Res 75(9):1828–1837

    CrossRef  CAS  PubMed  Google Scholar 

  41. Calligaris D, Caragacianu D, Liu X, Norton I, Thompson CJ, Richardson AL, Golshan M, Easterling ML, Santagata S, Dillon DA, Jolesz FA, Agar NYR (2014) Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis. Proc Natl Acad Sci U S A 111(42):15184–15189

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  42. Abbassi-Ghadi N, Veselkov K, Kumar S, Huang J, Jones E, Strittmatter N, Kudo H, Goldin R, Takats Z, Hanna GB (2014) Discrimination of lymph node metastases using desorption electrospray ionisation-mass spectrometry imaging. Chem Commun 50(28):3661–3664

    CrossRef  CAS  Google Scholar 

  43. Calligaris D, Norton I, Feldman DR, Ide JL, Dunn IF, Eberlin LS, Cooks RG, Jolesz FA, Golby AJ, Santagata S, Agar NY (2013) Mass spectrometry imaging as a tool for surgical decision-making. J Mass Spectrom 48(11):1178–1187

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ifa DR, Wiseman JM, Song Q, Cooks RG (2007) Development of capabilities for imaging mass spectrometry under ambient conditions with desorption electrospray ionization (DESI). Int J Mass Spectrom 259(1):8–15

    CrossRef  CAS  Google Scholar 

  45. Manicke NE, Kistler T, Ifa DR, Cooks RG, Ouyang Z (2009) High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 20(2):321–325

    CrossRef  CAS  PubMed  Google Scholar 

  46. Kiernan J (2015) Histological and Histochemical methods: theory and practice. Scion Publishing Limited, Banbury

    Google Scholar 

  47. Xiong X, Xu W, Eberlin LS, Wiseman JM, Fang X, Jiang Y, Huang Z, Zhang Y, Cooks RG, Ouyang Z (2012) Data processing for 3D mass spectrometry imaging. J Am Soc Mass Spectrom 23(6):1147–1156

    CrossRef  CAS  PubMed  Google Scholar 

  48. Kishton RJ, Rathmell JC (2015) Novel therapeutic targets of tumor metabolism. Cancer J 21(2):62–69

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  49. Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cheng L, Cooks RG (2011) Non-destructive, histologically compatible tissue imaging by desorption electrospray ionization mass spectrometry. Chembiochem 12(14):2129–2132

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  50. Hsu C-C, Chou P-T, Zare RN (2015) Imaging of proteins in tissue samples using nanospray desorption electrospray ionization mass spectrometry. Anal Chem 87(22):11171–11175

    CrossRef  CAS  PubMed  Google Scholar 

  51. Dakubo GD (2010) The Warburg phenomenon and other metabolic alterations of cancer cells. In: Mitochondrial genetics and cancer. Springer Berlin Heidelberg, Berlin, Heidelberg, pp 39–66. https://doi.org/10.1007/978-3-642-11416-8_2

    CrossRef  Google Scholar 

  52. Chambers MC, Maclean B, Burke R, Amodei D, Ruderman DL, Neumann S, Gatto L, Fischer B, Pratt B, Egertson J, Hoff K, Kessner D, Tasman N, Shulman N, Frewen B, Baker TA, Brusniak M-Y, Paulse C, Creasy D, Flashner L, Kani K, Moulding C, Seymour SL, Nuwaysir LM, Lefebvre B, Kuhlmann F, Roark J, Rainer P, Detlev S, Hemenway T, Huhmer A, Langridge J, Connolly B, Chadick T, Holly K, Eckels J, Deutsch EW, Moritz RL, Katz JE, Agus DB, MacCoss M, Tabb DL, Mallick P (2012) A cross-platform toolkit for mass spectrometry and proteomics. Nat Biotechnol 30:918

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  53. Race AM, Styles IB, Bunch J (2012) Inclusive sharing of mass spectrometry imaging data requires a converter for all. J Proteomics 75(16):5111–5112

    CrossRef  CAS  PubMed  Google Scholar 

  54. Robichaud G, Garrard KP, Barry JA, Muddiman DC (2013) MSiReader: an open-source interface to view and analyze high resolving power MS imaging files on Matlab platform. J Am Soc Mass Spectrom 24(5):718–721

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Authors are thankful to Prof. Richard N. Zare for his encouragement and advice. S.B. gratefully acknowledges the help from Dr. Livia S. Eberlin, Prof. Robert J. Tibshirani, Prof. James D. Brooks, Dr. Christian A. Kunder, Dr. Rosalie Nolley, Dr. Richard Fan, and Dr. Geoffrey A. Sonn. This work was supported by the Indian Institute of Science Education and Research, Tirupati, and Saha Institute of Nuclear Physics, Kolkata. S.B. is also thankful to Science and Engineering Research Board, Department of Science and Technology, Government of India, for providing Ramanujan Fellowship Research Grant (SB/S2/RJN-130/2017).

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Authors and Affiliations

  1. Indian Institute of Science Education and Research Tirupati, Tirupati, Andhra Pradesh, India

    Shibdas Banerjee

  2. Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics (HBNI), Kolkata, West Bengal, India

    Soumen Kanti Manna

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  1. Shibdas Banerjee
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  2. Soumen Kanti Manna
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Correspondence to Shibdas Banerjee .

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Editors and Affiliations

  1. National Cancer Institute, North Bethesda, MD, USA

    Dr. Majda Haznadar

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Banerjee, S., Manna, S.K. (2019). Assessment of Metabolic Signature for Cancer Diagnosis Using Desorption Electrospray Ionization Mass Spectrometric Imaging. In: Haznadar, M. (eds) Cancer Metabolism. Methods in Molecular Biology, vol 1928. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9027-6_15

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  • DOI: https://doi.org/10.1007/978-1-4939-9027-6_15

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