NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma

Article English OPEN
Rocha, CM ; Barros, AS ; Goodfellow, BJ ; Carreira, IM ; Gomes, AA ; Sousa, V ; Bernardo, J ; Carvalho, L ; Gil, AM ; Duarte, IF (2015)
  • Related identifiers: doi: 10.1093/carcin/bgu226
  • Subject: Carcinoma de Células Escamosas | Adenocarcinoma | Metabolómica | Espectroscopia de Ressonância Magnética | Neoplasias do Pulmão | Biomarcadores Tumorais

Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers. info:eu-repo/semantics/publishedVersion
  • References (48)
    48 references, page 1 of 5

    1. Ferlay,J. et  al. (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur. J. Cancer, 46, 765-781.

    2. Kerr,K.M. (2012) Personalized medicine for lung cancer: new challenges for pathology. Histopathology, 60, 531-546.

    3. Travis,W.D. et al. (2004). World Health Organization classicfiation of tumours; tumours of lung, pleura, thymus and heart. IARC Press, Lyon, France.

    4. Cooper,W.A. et  al. (2011) What's new in non-small cell lung cancer for pathologists: the importance of accurate subtyping, EGFR mutations and ALK rearrangements. Pathology, 43, 103-115.

    5. Warth,A. et al. (2012) Large-scale comparative analyses of immunomarkers for diagnostic subtyping of non-small-cell lung cancer biopsies. Histopathology, 61, 1017-1025.

    6. Hanahan,D. et al. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646-674.

    7. Mazurek,S. (2007) Tumour cell energetic metabolome. In: Saks,V. (ed) Molecular System Bioenergetic: Energy for Life. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, pp. 521-540.

    8. Cantor,J.R. et  al. (2012) Cancer cell metabolism: one hallmark, many faces. Cancer Discov., 2, 881-898.

    9. Moestue,S. et al. (2011) HR MAS MR spectroscopy in metabolic characterization of cancer. Curr. Top. Med. Chem., 11, 2-26.

    10. Rocha,C.M. et al. (2010) Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. J. Proteome Res., 9, 319-332.

  • Metrics
    0
    views in OpenAIRE
    3
    views in local repository
    1
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Repositório Institucional dos Hospitais da Universidade de Coimbra 3 1
Share - Bookmark