Analytical and Bioanalytical Chemistry

, Volume 405, Issue 15, pp 5013–5030 | Cite as

Metabolomics of colorectal cancer: past and current analytical platforms

  • Michael D. Williams
  • Raymond Reeves
  • Linda S. Resar
  • Herbert H. HillJr.
Review

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.

Abstract Figure

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

Keywords

Bioanalytical methods Mass spectrometry/inductively coupled plasma mass spectrometry Nuclear magnetic resonance/electron spin resonance High-performance liquid chromatography Gas chromatography Capillary electrophoresis/electrophoresis 

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

Supplementary material

216_2013_6777_MOESM1_ESM.pdf (223 kb)
ESM 1(PDF 223 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Michael D. Williams
    • 1
  • Raymond Reeves
    • 2
  • Linda S. Resar
    • 3
  • Herbert H. HillJr.
    • 1
  1. 1.Department of ChemistryWashington State UniversityPullmanUSA
  2. 2.School of Molecular BiosciencesWashington State UniversityPullmanUSA
  3. 3.Hematology DivisionJohns Hopkins University School of MedicineBaltimoreUSA

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