title: NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma.
abstract: 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.
authors.affiliation: CICECO, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, QOPNA Research Unit, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and Cardiothoracic Surgery, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal.
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Rocha
authors.affiliation: QOPNA Research Unit, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: António S
authors.initials: AS
authors.lastname: Barros
authors.affiliation: CICECO, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, QOPNA Research Unit, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and Cardiothoracic Surgery, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.affiliation: Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira
authors.affiliation: Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Gomes
authors.affiliation: Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and.
authors.forename: Vitor
authors.initials: V
authors.lastname: Sousa
authors.affiliation: Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and Cardiothoracic Surgery, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Bernardo
authors.affiliation: Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and.
authors.forename: Lina
authors.initials: L
authors.lastname: Carvalho
authors.affiliation: CICECO, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, QOPNA Research Unit, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and Cardiothoracic Surgery, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
authors.affiliation: CICECO, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, QOPNA Research Unit, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal, Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal, Centre for Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, Department of Pathological Anatomy, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal, Institute of Pathological Anatomy, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal and Cardiothoracic Surgery, University Hospitals of Coimbra, 3000-075 Coimbra, Portugal ioladuarte@ua.pt.
authors.forename: Iola F
authors.initials: IF
authors.lastname: Duarte
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor