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Metabolomics of colorectal cancer: past and current analytical platforms

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Abstract

Metabolomics is coming of age as an important area of investigation which may help reveal answers to questions left unanswered or only partially understood from proteomic or genomic approaches. Increased knowledge of the relationship of genes and proteins to smaller biomolecules (metabolites) will advance our ability to diagnose, treat, and perhaps prevent cancer and other diseases that have eluded scientists for generations. Colorectal tumors are the second leading cause of cancer mortality in the USA, and the incidence is rising. Many patients present late, after the onset of symptoms, when the tumor has spread from the primary site. Once metastases have occurred, the prognosis is significantly worse. Understanding alterations in metabolic profiles that occur with tumor onset and progression could lead to better diagnostic tests as well as uncover new approaches to treat or even prevent colorectal cancer (CRC). In this review, we explore the various analytical technologies that have been applied in CRC metabolomics research and summarize all metabolites measured in CRC and integrate them into metabolic pathways. Early studies with nuclear magnetic resonance and gas-chromatographic mass spectrometry suggest that tumor cells are characterized by aerobic glycolysis, increased purine metabolism for DNA synthesis, and protein synthesis. Liquid chromatography, capillary electrophoresis, and ion mobility, each coupled with mass spectrometry, promise to advance the field and provide new insight into metabolic pathways used by cancer cells. Studies with improved technology are needed to identify better biomarkers and targets for treatment or prevention of CRC.

2D IMMS spectra of Tumor and normal matched tissues. Several metabolites are detected within the bracketed area in only the Tumor sample.

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Abbreviations

ASL:

Arginosuccinate lyase

ATP:

Adenosine triphosphate

CE:

Capillary electrophoresis

CRC:

Colorectal cancer

ESI:

Electrospray ionization

FTICR:

Fourier transform ion cyclotron resonance

GC:

Gas chromatography

GPAM:

Mitochondrial glycerol 3-phosphate acyltransferase

2-HG:

2-Hydroxyglutarate

HMGA1:

High mobility group A1

HRMAS-NMR:

High-resolution magic-angle-spinning 1H nuclear magnetic resonance

IDH:

Isocitrate dehydrogenase

IMMS:

Ion mobility mass spectrometry

IMS:

Ion mobility spectrometry

LC:

Liquid chromatography

mCRC:

Metastatic colorectal cancer

MS/MS:

Tandem mass spectrometry

NMR:

Nuclear magnetic resonance

OPLS-DA:

Orthogonal partial least squares discriminant analysis

PCA:

Principal component analysis

PLS-DA:

Partial least squares discriminant analysis

TCA:

Tricarboxylic acid

TOFMS:

Time-of-flight mass spectrometry

TWIMMS:

Traveling wave ion mobility mass spectrometry

UPLC:

Ultraperformance liquid chromatography

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  1. Department of Chemistry, Washington State University, Pullman, WA, 99164, USA

    Michael D. Williams & Herbert H. Hill Jr.

  2. School of Molecular Biosciences, Washington State University, Pullman, WA, 99164, USA

    Raymond Reeves

  3. Hematology Division, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Linda S. Resar

Authors
  1. Michael D. Williams
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  2. Raymond Reeves
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  3. Linda S. Resar
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  4. Herbert H. Hill Jr.
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Correspondence to Herbert H. Hill Jr..

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Published in the topical collection Metabolomics and Metabolite Profiling with guest editors Rainer Schuhmacher, Rudolf Krska, Roy Goodacre and Wolfram Weckwerth.

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Williams, M.D., Reeves, R., Resar, L.S. et al. Metabolomics of colorectal cancer: past and current analytical platforms. Anal Bioanal Chem 405, 5013–5030 (2013). https://doi.org/10.1007/s00216-013-6777-5

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  • DOI: https://doi.org/10.1007/s00216-013-6777-5

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