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

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjec...

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Bibliographic Details
Published in:Journal of proteome research 2011-09, Vol.10 (9), p.4314-4324
Main Authors: Rocha, Cláudia M, Carrola, Joana, Barros, António S, Gil, Ana M, Goodfellow, Brian J, Carreira, Isabel M, Bernardo, João, Gomes, Ana, Sousa, Vitor, Carvalho, Lina, Duarte, Iola F
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Blood Glucose
Female
Humans
Lactic Acid - blood
Lipoproteins - blood
Lung Neoplasms - blood
Lung Neoplasms - chemistry
Male
Metabolome
Metabolomics
Middle Aged
Monte Carlo Method
Nuclear Magnetic Resonance, Biomolecular
Reproducibility of Results
ROC Curve
Valine - blood
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Summary:In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients’ plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr200550p