abstract
This work aims at characterizing the metabolic profile of human lung cancer, to gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic value in the future. Paired samples of tumor and noninvolved adjacent tissues from 12 lung tumors have been directly analyzed by H-1 HRMAS NMR (500/600 MHz) enabling, for the first time to our knowledge, the identification of over 50 compounds. The effect of temperature on tissue stability during acquisition time has also been investigated, demonstrating that analysis should be performed within less than two hours at low temperature (277 K), to minimize glycerophosphocholine (GPC) and phosphocholine (PC) conversion to choline and reduce variations in some amino acids. The application of Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) to the standard 1D H-1 spectra resulted in good separation between tumor and control samples, showing that inherently different metabolic signatures characterize the two tissue types. On the basis of spectral integration measurements, lactate, PC, and GPC were found to be elevated in tumors, while glucose, myo-inositol, inosine/adenosine, and acetate were reduced. These results show the valuable potential of HRMAS NMR-metabonomics for investigating the metabolic phenotype of lung cancer.
keywords
MAGNETIC-RESONANCE-SPECTROSCOPY; PERCHLORIC-ACID EXTRACTS; HR-MAS SPECTROSCOPY; INVASIVE CERVICAL-CANCER; BREAST-CANCER; IN-VIVO; H-1-NMR SPECTROSCOPY; PATTERN-RECOGNITION; PROSTATE-CANCER; BRAIN-TUMORS
subject category
Biochemistry & Molecular Biology
authors
Rocha, CM; Barros, AS; Gil, AM; Goodfellow, BJ; Humpfer, E; Spraul, M; Carreira, IM; Melo, JB; Bernardo, J; Gomes, A; Sousa, V; Carvalho, L; Duarte, IF
our authors
Ana Maria Pissarra Coelho Gil
Associate Professor with Aggregation
António de Sousa Barros
Post-doc Fellowship
Brian James Goodfellow
Assistant Professor
Iola Melissa Fernandes Duarte
Principal Researcheracknowledgements
Funding is acknowledged from the Foundation for Science and Technology (FCT), Portugal, through the research project FCT/PTDC/QUI/68017/2006 and from CIMAGO, University of Coimbra (project 14/06). I.F.D. further acknowledges L'Oreal Portugal, FCT and the National UNESCO Committee for funding this work through the