Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS).
Current clinical strategy for staging and prognostication of colorectal cancer (CRC) relies mainly upon the TNM or Duke system. This clinicopathological stage is a crude prognostic guide because it reflects in part the delay in diagnosis in the case of an advanced cancer and gives little insight into the biological characteristics of the tumor. We hypothesized that global metabolic profiling (metabonomics/metabolomics) of colon mucosae would define metabolic signatures that not only discriminate malignant from normal mucosae, but also could distinguish the anatomical and clinicopathological characteristics of CRC. We applied both high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) and gas chromatography mass spectrometry (GC/MS) to analyze metabolites in biopsied colorectal tumors and their matched normal mucosae obtained from 31 CRC patients. Orthogonal partial least-squares discriminant analysis (OPLS-DA) models generated from metabolic profiles obtained by both analytical approaches could robustly discriminate normal from malignant samples (Q(2) > 0.50, Receiver Operator Characteristic (ROC) AUC >0.95, using 7-fold cross validation). A total of 31 marker metabolites were identified using the two analytical platforms. The majority of these metabolites were associated with expected metabolic perturbations in CRC including elevated tissue hypoxia, glycolysis, nucleotide biosynthesis, lipid metabolism, inflammation and steroid metabolism. OPLS-DA models showed that the metabolite profiles obtained via HR-MAS NMR could further differentiate colon from rectal cancers (Q(2)> 0.60, ROC AUC = 1.00, using 7-fold cross validation). These data suggest that metabolic profiling of CRC mucosae could provide new phenotypic biomarkers for CRC management.
Chan
Eric Chun Yong
EC
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Koh
Poh Koon
PK
Mal
Mainak
M
Cheah
Peh Yean
PY
Eu
Kong Weng
KW
Backshall
Alexandra
A
Cavill
Rachel
R
Nicholson
Jeremy K
JK
Keun
Hector C
HC
D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D011379:Prognosis; D012372:ROC Curve; D012007:Rectum / Q000473:pathology; D015203:Reproducibility of Results
D015415:Biomarkers