Metabolic Profiling of Human Lung Cancer Tissue by 1H High Resolution Magic Angle Spinning (HRMAS) NMR Spectroscopy

被引:127
|
作者
Rocha, Claudia M. [1 ]
Barros, Antonio S. [2 ]
Gil, Ana M. [1 ]
Goodfellow, Brian J. [1 ,3 ]
Humpfer, Eberhard [4 ]
Spraul, Manfred [4 ]
Carreira, Isabel M. [3 ,5 ,6 ]
Melo, Joana B. [5 ,6 ]
Bernardo, Joao [3 ,7 ]
Gomes, Ana [3 ,7 ]
Sousa, Vitor [3 ,7 ]
Carvalho, Lina [3 ,7 ]
Duarte, Iola F. [1 ,3 ]
机构
[1] Univ Aveiro, Dept Chem, CICECO, P-3810193 Aveiro, Portugal
[2] Univ Aveiro, Dept Chem, QOPNA, P-3810193 Aveiro, Portugal
[3] Univ Coimbra, Fac Med, CIMAGO, P-3000 Coimbra, Portugal
[4] Bruker BioSpin GmbH, D-76287 Rheinstetten, Germany
[5] Univ Coimbra, Fac Med, Cytogenet Lab, P-3000 Coimbra, Portugal
[6] Univ Coimbra, Fac Med, CNC, P-3000 Coimbra, Portugal
[7] Univ Coimbra, Fac Med, Inst Pathol Anat, P-3000 Coimbra, Portugal
关键词
lung cancer; NMR spectroscopy; HRMAS; metabolic composition; multivariate analysis; PERCHLORIC-ACID EXTRACTS; MAGNETIC-RESONANCE-SPECTROSCOPY; INVASIVE CERVICAL-CANCER; HR-MAS SPECTROSCOPY; BREAST-CANCER; H-1-NMR SPECTROSCOPY; IN-VITRO; PATTERN-RECOGNITION; PROSTATE-CANCER; BIOPSY;
D O I
10.1021/pr9006574
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:319 / 332
页数:14
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