Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Urine

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Carrola, J (Author) Other; Rocha, CM (Author) Other; Barros, AS (Author) Other; Gil, AM (Author) Other; Goodfellow, BJ (Author) Other; Carreira, IM (Author) Other; Bernardo, J (Author) Other; Gomes, A (Author) Other; Sousa, V (Author) Other; Carvalho, L (Author) Other; Duarte, IF (Author) Other

Journal

Title: Journal of Proteome Research

Vol. 10

Pages: 221-230

ISSN: 1535-3893

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 196 Citations

Scopus - 203 Citations

Other information

Authenticus ID: P-002-Z0J

DOI: 10.1021/pr100899x

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10