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Can nuclear magnetic resonance (NMR) spectroscopy reveal different metabolic signatures for lung tumours?

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Abstract

This study aims to evaluate the potential of 1H NMR spectroscopy, combined with multivariate statistics, for discriminating between tumour and non-involved (control) pulmonary parenchyma and for providing biochemical information on different histological types. Paired tissue samples from 24 primary lung tumours were directly analysed by high-resolution magic angle spinning (HRMAS) 1H NMR spectroscopy (500 MHz), and their spectral profiles subjected to principal component analysis (PCA) and partial least squares regression discriminant analysis (PLS-DA). Tumour and adjacent control parenchyma were clearly discriminated in the PLS-DA model with a high level of sensitivity (95% of tumour samples correctly classified) and 100% specificity (no false positives). The metabolites giving rise to this separation were mainly lactate, glycerophosphocholine, phosphocholine, taurine, reduced glutathione and uridine di-phosphate (elevated in tumours) and glucose, phosphoethanolamine, acetate, lysine, methionine, glycine, myo- and scyllo-inositol (reduced in tumours compared to control tissues). Furthermore, PLS-DA of a sub-set of tumour samples allowed adenocarcinomas to be discriminated from carcinoid tumours and epidermoid carcinomas, highlighting differences in metabolite levels between these histological types, and therefore revealing valuable knowledge on the biochemistry of different types of bronchial-pulmonary carcinomas.

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References

  1. Griffin JL, Shockor JP (2004) Metabolic profiles of cancer cells. Nat Rev Cancer 4:551–561

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Merz AL, Serkova NJ (2009) Use of nuclear magnetic resonance-based metabonomics in detecting drug resistance in cancer. Biomark Med 3:289–306

    Article  CAS  PubMed  Google Scholar 

  4. Sitter B, Bathen TF, Tessem M-B, Gribbestad IS (2009) High-resolution magic angle spinning (HR MAS) MR spectroscopy in metabolic characterization of human cancer. Prog Nucl Magn Reson Spectrosc 54:239–254

    Article  CAS  Google Scholar 

  5. Hanaoka H, Yoshioka Y, Ito I, Niitu K, Yasuda N (1993) In vitro characterization of lung cancers by the use of 1H nuclear magnetic resonance spectroscopy of tissue extracts and discriminant factor analysis. Magn Reson Med 29:436–440

    Article  CAS  PubMed  Google Scholar 

  6. Guo JF, Higashi K, Yokota H, Nagao Y, Ueda Y, Kodama Y, Oguchi M, Taki S, Tonami H, Yamamoto I (2004) In vitro proton magnetic resonance spectroscopic lactate and choline measurements, 18F-FDG uptake, and prognosis in patients with lung adenocarcinoma. J Nucl Med 45:1334–1339

    CAS  PubMed  Google Scholar 

  7. Yokota H, Guo J, Matoba M, Higashi K, Tonami H, Nagao Y (2007) Lactate, choline and creatine levels measured by vitro 1H-MRS as prognostic parameters in patients with non-small-cell lung cancer. J Magn Reson Imaging 25:992–999

    Article  PubMed  Google Scholar 

  8. Fan TW-M, Lane AN, Higashi RM, Bousamra M, Kloecker G, Miller DM (2009) Metabolic profiling identifies lung tumour responsiveness to erlotinib. Exp Mol Pathol 87:83–86

    Article  CAS  PubMed  Google Scholar 

  9. Fan TW-M, Lane AN, Higashi RM, Farag MA, Gao H, Bousamra M, Miller DM (2009) Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM). Mol Cancer 8:41

    Article  PubMed  Google Scholar 

  10. Swanson MG, Vigneron DB, Tabatabai ZL, Males RG, Schmitt L, Carroll PR, James JK, Hurd RE, Kurhanewicz J (2003) Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues. Magn Reson Med 50:944–954

    Article  CAS  PubMed  Google Scholar 

  11. Tugnoli V, Schenetti L, Mucci A, Parenti F, Cagnoli R, Righi V, Trinchero A, Nocetti L, Toraci C, Mavilla L, Trentini G, Zunarelli E, Tosi MR (2006) Ex vivo HR-MAS MRS of human meningiomas: a comparison with in vivo 1H MR spectra. Int J Mol Med 18:859–869

    CAS  PubMed  Google Scholar 

  12. Mountford C, Lean C, Malycha P, Russell P (2006) Proton spectroscopy provides accurate pathology on biopsy and in vivo. J Magn Reson Imaging 24:459–477

    Article  PubMed  Google Scholar 

  13. Thomas MA, Lipnick S, Velan SS, Liu X, Banakar S, Binesh N, Ramadan S, Ambrosio A, Raylman RR, Sayre J, DeBruhl N, Bassett L (2009) Investigation of breast cancer using two-dimensional MRS. NMR Biomed 22:77–91

    Article  CAS  PubMed  Google Scholar 

  14. Wilson M, Davies NP, Grundyd RG, Peet AC (2009) A quantitative comparison of metabolite signals as detected by in vivo MRS with ex vivo 1H HR-MAS for childhood brain tumours. NMR Biomed 22:213–219

    Article  CAS  PubMed  Google Scholar 

  15. Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE, Gribbestad IS (2006) Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed 19:30–40

    Article  CAS  PubMed  Google Scholar 

  16. Bathen TF, Jensen LR, Sitter B, Fjosne HE, Halgunset J, Axelson DE, Gribbestad IS, Lundgren S (2007) MR-determined metabolic phenotype of breast cancer in prediction of lymphatic spread, grade, and hormone status. Breast Cancer Res Treat 104:181–189

    Article  PubMed  Google Scholar 

  17. Erb G, Elbayed K, Piotto M, Raya J, Neuville A, Mohr M, Maitrot D, Kehrli P, Namer IJ (2008) Toward improved grading of malignancy in oligodendrogliomas using metabolomics. Magn Reson Med 59:959–965

    Article  CAS  PubMed  Google Scholar 

  18. Monleon D, Morales JM, Gonzalez-Darder J, Talamantes F, Cortes O, Gil-Benso R, Lopez-Gines C, Cerda-Nicolas M, Celda B (2008) Benign and atypical meningioma metabolic signatures by high-resolution magic-angle spinning molecular profiling. J Proteome Res 7:2882–2888

    Article  CAS  PubMed  Google Scholar 

  19. Cheng LL, Burns MA, Taylor JL, He W, Halpern EF, McDougal WS, Wu C-L (2005) Metabolic characterization of human prostate cancer with tissue magnetic resonance spectroscopy. Cancer Res 65:3030–3034

    CAS  PubMed  Google Scholar 

  20. Tessem M-B, Swanson MG, Keshari KR, Albers MJ, Joun D, Tabatabai ZL, Simko JP, Shinohara K, Nelson SJ, Vigneron DB, Gribbestad IS, Kurhanewicz J (2008) Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues. Magn Reson Med 60:510–516

    Article  CAS  PubMed  Google Scholar 

  21. van Asten JJA, Cuijpers V, Hulsbergen-van de Kaa C, Soede-Huijbregts C, Witjes JA, Verhofstad A, Heerschap A (2008) High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies. Magma 21:435–442

    Article  PubMed  Google Scholar 

  22. Sitter B, Bathen TF, Hagen B, Arentz C, Skjeldestad FE, Gribbestad IS (2004) Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy. Magma 16:174–181

    Article  CAS  PubMed  Google Scholar 

  23. Mahon MM, deSouza NM, Dina R, Soutter WP, McIndoe GA, Williams AD, Co IJ (2004) Preinvasive and invasive cervical cancer: an ex vivo proton magic angle spinning magnetic resonance spectroscopy study. NMR Biomed 17:144–153

    Article  PubMed  Google Scholar 

  24. De Silva SS, Payne GS, Thomas V, Carter PG, Ind TEJ, deSouza NM (2009) Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using 1H and 31P magic angle spinning MRS of intact tissue. NMR Biomed 22:191–198

    Article  PubMed  Google Scholar 

  25. Chan ECY, Koh PK, Mal M, Cheah PY, Eu KW, Backshall A, Cavill R, Nicholson JK, Keun HC (2009) Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res 8:352–361

    Article  CAS  PubMed  Google Scholar 

  26. Piotto M, Moussallieh F-M, Dillmann B, Imperiale A, Neuville A, Brigand C, Bellocq J-P, Elbayed K, Namer IJ (2009) Metabolic characterization of primary human colorectal cancers using high resolution magic angle spinning 1H magnetic resonance spectroscopy. Metabolomics 5:292–301

    Article  CAS  Google Scholar 

  27. Yang Y, Li C, Nie X, Feng X, Chen W, Yue Y, Tang H, Deng F (2007) Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis. J Proteome Res 6:2605–2614

    Article  CAS  PubMed  Google Scholar 

  28. Tate AR, Foxall PJD, Holmes E, Moka D, Spraul M, Nicholson JK, Lindon JC (2000) Distinction between normal and renal cell carcinoma kidney cortical biopsy samples using pattern recognition of 1H magic angle spinning (MAS) NMR spectra. NMR Biomed 13:64–71

    Article  CAS  PubMed  Google Scholar 

  29. Righi V, Mucci A, Schenetti L, Tosi MR, Grigioni WF, Corti B, Bertaccini A, Franceschelli A, Sanguedolce F, Schiavina R, Martorana G, Tugnoli V (2007) Ex vivo HR-MAS magnetic resonance spectroscopy of normal and malignant human renal tissues. Anticancer Res 27:3195–3204

    CAS  PubMed  Google Scholar 

  30. Tugnoli V, Mucci A, Schenetti L, Righi V, Calabrese C, Fabbri A, Di Febo G, Tosi MR (2006) Ex vivo HR-MAS magnetic resonance spectroscopy of human gastric adenocarcinomas: a comparison with healthy gastric mucosa. Oncol Rep 16:543–553

    CAS  PubMed  Google Scholar 

  31. Jordan KW, Adkins CB, Su L, Halpern EF, Mark EJ, Christiani DC, Cheng LL (2009) Comparison of squamous cell carcinoma and adenocarcinoma of the lung by metabolomic analysis of tissue–serum pairs. Lung Cancer 68:44–50

    Article  PubMed  Google Scholar 

  32. Rocha CM, Barros AS, Gil AM, Goodfellow BJ, Humpfer E, Spraul M, Carreira IM, Melo JB, Bernardo J, Gomes A, Sousa V, Carvalho L, Duarte IF (2010) Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. J Proteome Res 9:319–332

    Article  CAS  PubMed  Google Scholar 

  33. Travis WD, Brambilla E, Müller-Hermelink HK, Harris C (2004) World Health Organization Classification of Tumours: tumours of the lung, pleura, thymus and heart. IARC Press, Lyon

    Google Scholar 

  34. Xu Q-S, Liang Y-Z (2001) Monte Carlo cross validation. Chemometr Intell Lab Syst 56:1–11

    Article  CAS  Google Scholar 

  35. Glunde K, Ackerstaff E, Mori N, Jacobs MA, Bhujwalla ZM (2006) Choline phospholipid metabolism in cancer: consequences for molecular pharmaceutical interventions. Mol Pharm 3:496–506

    Article  CAS  PubMed  Google Scholar 

  36. Balendiran GK, Dabur R, Fraser D (2004) The role of glutathione in cancer. Cell Biochem Funct 22:343–352

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Funding is acknowledged from the Foundation for Science and Technology (FCT), Portugal, and FEDER (research project FCT/PTDC/QUI/68017/2006; FCOMP-01-0124-FEDER-007439) and from CIMAGO, University of Coimbra (project 14/06). C.R. further acknowledges FCT for the doctoral grant SFRH/BD/63430/2009, and IFD acknowledges L’Oréal Portugal, FCT and the National UNESCO Committee for funding this work through the L’Oréal Medals of Honor for Women in Science 2007.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. CICECO, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Iola F. Duarte, Cláudia M. Rocha, Ana M. Gil & Brian J. Goodfellow

  2. QOPNA, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    António S. Barros

  3. Cytogenetics Laboratory and CNC, Faculty of Medicine, University of Coimbra, 3000, Coimbra, Portugal

    Isabel M. Carreira

  4. University Hospitals of Coimbra, 3000-075, Coimbra, Portugal

    João Bernardo, Ana Gomes, Vitor Sousa & Lina Carvalho

  5. Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, 3000, Coimbra, Portugal

    Vitor Sousa & Lina Carvalho

  6. CIMAGO, Faculty of Medicine, University of Coimbra, 3000, Coimbra, Portugal

    Iola F. Duarte, Brian J. Goodfellow, Isabel M. Carreira, João Bernardo, Ana Gomes, Vitor Sousa & Lina Carvalho

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  1. Iola F. Duarte
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  2. Cláudia M. Rocha
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Correspondence to Iola F. Duarte.

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Duarte, I.F., Rocha, C.M., Barros, A.S. et al. Can nuclear magnetic resonance (NMR) spectroscopy reveal different metabolic signatures for lung tumours?. Virchows Arch 457, 715–725 (2010). https://doi.org/10.1007/s00428-010-0993-6

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  • DOI: https://doi.org/10.1007/s00428-010-0993-6

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