Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Urine
authors Carrola, J; Rocha, CM; Barros, AS; Gil, AM; Goodfellow, BJ; Carreira, IM; Bernardo, J; Gomes, A; Sousa, V; Carvalho, L; Duarte, IF
nationality International
journal JOURNAL OF PROTEOME RESEARCH
author keywords lung cancer; NMR spectroscopy; metabonomics; urine; metabolic profile
keywords NUCLEAR-MAGNETIC-RESONANCE; H-1-NMR SPECTROSCOPY; MASS-SPECTROMETRY; BLADDER-CANCER; PROGRESSION; BIOMARKER; SARCOSINE; PROFILES; TUMORS
abstract In this study, H-1 NMR-based metabonomics has been applied, for the first time to our knowledge, to investigate lung cancer metabolic signatures in urine, aiming at assessing the diagnostic potential of this approach and gaining novel insights into lung cancer metabolism and systemic effects. Urine samples from lung cancer patients (n = 71) and a control healthy group (n = 54) were analyzed by high resolution H-1 NMR (500 MHz), and their spectral profiles subjected to multivariate statistics, namely, Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Projections to Latent Structures (OPLS)-DA. Very good discrimination between cancer and control groups was achieved by multivariate modeling of urinary profiles. By Monte Carlo Cross Validation, the classification model showed 93% sensitivity, 94% specificity and an overall classification rate of 93.5%. The possible confounding influence of other factors, namely, gender and age, have also been modeled and found to have much lower predictive power than the presence of the disease. Moreover, smoking habits were found not to have a dominating influence over class discrimination. The main metabolites contributing to this discrimination, as highlighted by multivariate analysis and confirmed by spectral integration, were hippurate and trigonelline (reduced in patients), and beta-hy-droxyisovalerate, alpha-hydroxyisobutyrate, N-acetylglutamine, and creatinine (elevated in patients relatively to controls). These results show the valuable potential of NMR-based metabonomics for finding putative biomarkers of lung cancer in urine, collected in a minimally invasive way, which may have important diagnostic impact, provided that these metabolites are found to be specifically disease-related.
publisher AMER CHEMICAL SOC
issn 1535-3893
year published 2011
volume 10
issue 1
beginning page 221
ending page 230
digital object identifier (doi) 10.1021/pr100899x
web of science category Biochemical Research Methods
subject category Biochemistry & Molecular Biology
unique article identifier WOS:000285812000027
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journal impact factor 4.074
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