title: Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy.
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 (1)H 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 (1)H 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.
authors.affiliation: CICECO, Department of Chemistry, University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Rocha
authors.forename: António S
authors.initials: AS
authors.lastname: Barros
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.forename: Eberhard
authors.initials: E
authors.lastname: Humpfer
authors.forename: Manfred
authors.initials: M
authors.lastname: Spraul
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Carreira
authors.forename: Joana B
authors.initials: JB
authors.lastname: Melo
authors.forename: João
authors.initials: J
authors.lastname: Bernardo
authors.forename: Ana
authors.initials: A
authors.lastname: Gomes
authors.forename: Vitor
authors.initials: V
authors.lastname: Sousa
authors.forename: Lina
authors.initials: L
authors.lastname: Carvalho
authors.forename: Iola F
authors.initials: IF
authors.lastname: Duarte
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D025341:Principal Component Analysis