Metabolic profiling of colorectal cancer and polyps using NMR, and advanced MS methods
Abstract
Metabolic profiling, or metabolomics, has emerged as a promising field for its potential in disease diagnosis, prognosis, personalized therapy, and valuable insights into pathogenesis and systems biology. Nuclear magnetic resonance (NMR) and chromatography coupled mass spectrometry (MS) are the main analytical techniques used in metabolomics because they provide for the identification and quantification of a large number of metabolites in complex biological samples. The analysis of the information rich datasets from large-scale sample populations is facilitated by advanced statistical methods including feature selection and discriminative model construction. This work mainly focuses on metabolite profiling studies of colorectal cancer. Using the complementary information provided by global NMR and MS based metabolite profiling, a series of serum metabolite biomarkers were discovered. The underlying correlations of specific metabolite levels with oncologic development were studied. The up-regulation of glycolysis and glutaminolysis were found to be correlated with the presence of colorectal cancer. Lower abundances of many amino acids were also found in the serum samples from cancerous patients. Similar trends in these metabolic perturbations were discovered in the sera from patients with adenomatous polyps compared to healthy controls, except that glucose was down-regulated in patients with adenomatous polyps and up-regulated in the serum of patients with colorectal cancer. The combination of the NMR and MS data provided for improved and cross validated statistical models. The studies described here indicate a good potential for the development of metabolite profiles for colon cancer detection and at risk patient identification.
Degree
Ph.D.
Advisors
Raftery, Purdue University.
Subject Area
Analytical chemistry
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