Summary
Metabolomics, one of the “omic” sciences in systems biology, is the global assessment and validation of endogenous small-molecule biochemicals (metabolites) within a biologic system. Initially, putative quantitative metabolic biomarkers for cancer detection and/or assessment of efficacy of anticancer treatment are usually discovered in a preclinical setting (using animal and human cell cultures), followed by translational validation of these biomarkers in biofluid or tumor tissue. Based on the tumor origin, various biofluids, such as blood, urine, and expressed prostatic secretions, can be used for validating metabolic biomarkers noninvasively in cancer patients. Metabolite detection and quantification is usually carried out by nuclear magnetic resonance (NMR) spectroscopy, while mass spectrometry (MS) provides another highly sensitive metabolomics technology. Usually, sophisticated statistical analyses are carried out either on spectroscopic or on quantitative metabolic data sets to provide meaningful information about the metabolic makeup of the sample. Various metabolic biomarkers, related to glycolysis, mitochondrial citric cycle acid, choline and fatty acid metabolism, were recently reported to play important roles in cancer development and responsiveness to anticancer treatment using NMR-based metabolic profiling.
Carefully designed and validated protocols for sample handling and sample extraction followed by appropriate NMR techniques and statistical analyses, which are required to establish quantitative 1H-NMR-based metabolomics as a reliable analytical tool in the area of cancer biomarker discovery, are discussed in the present chapter.
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Acknowledgments
The authors would like to thank Jaimi L. Brown, B.S., for her continuous help in developing and validating sample preparation protocols, as well as Dr. Eduard J. Gamito for his help with statistical methods. This work was supported by the National Institutes of Health grants R21 CA112216 (KG), P50 CA103175 (JHU ICMIC Program, KG), R21 CA108624 (NJS) and P30 CA046934 (NJS).
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Serkova, N.J., Glunde, K. (2009). Metabolomics of Cancer. In: Tainsky, M. (eds) Tumor Biomarker Discovery. Methods in Molecular Biology, vol 520. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-811-9_20
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DOI: https://doi.org/10.1007/978-1-60327-811-9_20
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