Differential diagnosis by metabolic profile: a dream or reality?

Abstract

. ualitative and quantitative measurement and interpreItation of metabolic profile in health and disease are the current area of research and are a recent progression ñ'om t ^ studies of genomics and proteomics. Advanced analytical technologies including high-performance liquid chromatography gas chromatography (GC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy either alone or in combination are being widely used to analyze samples from natural sources, including tissues and biofiuids. Chemometrics, a system of statistical analytical applications, is used to evaluate and understand the complex data derived from these experiments. A quick look at current research on metabolomics will show studies involving every human organ system, including prediction of embryo implantation based on spent culture medium fi'om in vitro fertilization. There are also studies on discovery of new chemicals and analyses of the structure of such new chemicals. Human metabolomic studies aim to develop metabolic profiles of diseases wdth the hope that such multiparameter profiles may help to more accurately diagnose specific disease processes than a single biomarker. Metabolomic research is being applied to study of both chronic and acute illnesses. Some examples wiU be highlighted here. In oncologic research, application of the above technologies has yielded promising results. In 1993, Schiebler et al (1), using 'H NMR spectroscopy of prostate tissue, demonstrated the metabolic profiles of normal prostate, benign prostatic hyperplasia, and adenocarcinoma. Their work demonstrated that depressed levels of citrate in adenocarcinoma may be the discriminating factor. Sitter et al (2) studied breast cancer tissue from 85 patients along with adjacent uninvolved tissue in 18 of these patients using high-resolution magic-angle-spinning NMR spectroscopy. The resulting spectra were examined by three different approaches: 1) Relative intensities of glycerophosphocholine (GPC), phosphocholine (PC), and choline were compared for cancerous and uninvolved specimens. 2) Eight metabolites, choline, creatine, ß-glucose, GPC, glycine, myo-inositol, PC, and taurine, were quantified from the recorded spectra and compared with tumor histological type and size, patient's lymph node status, and tissue composition of the

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