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, 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.




Biochemistry & Molecular Biology


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

nossos autores


Funding is acknowledged from the European Regional Development Fund through the Competitive Factors Thematic Operational Programme and from the Foundation for Science and Technology (FCT), Portugal (research project FCT/PTDC/QUI/68017/2006; FCOMP-01-0124-FEDER-007439). C.M.R further acknowledges FCT for the doctoral grant SFRH/BD/63430/2009, and I.F.D. acknowledges L'Oreal Portugal, FCT, and the National UNESCO Committee for funding this work through the L'Oreal Medals of Honor for Women in Science 2007. The Portuguese National NMR Network (RNRMN), supported with FCT funds, is also acknowledged. The authors are grateful to all the volunteers who participated in this study, as well as to Dr. Jorge Ferreira and Eng. Nelson Ramos from INDASA S.A. for collaboration in the collection of control samples. Finally, Bruker BioSpin GmbH is acknowledged for access to BBIOREFCODE.

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