Abstract
Untargeted metabolomics is expected to lead to a better mechanistic understanding of diseases and thus applications of precision medicine and personalized intervention. To further increase metabolite coverage and achieve high accuracy of metabolite quantification, the present proof-of-principle study was to explore the applicability of integration of two-dimensional gas and liquid chromatography-mass spectrometry (GC × GC-MS and 2DLC-MS) platforms to characterizing circulating polar metabolome extracted from plasma collected from 29 individuals with colorectal cancer in comparison with 29 who remained cancer-free. After adjustment of multiple comparisons, 20 metabolites were found to be up-regulated and 8 metabolites were found to be down-regulated, which pointed to the dysregulation in energy metabolism and protein synthesis. While integrating the GC × GC-MS and 2DLC-MS data can dramatically increase the metabolite coverage, this study had a limitation in analyzing the non-polar metabolites. Given the small sample size, these results need to be validated with a larger sample size and with samples collected prior to diagnostic and treatment. Nevertheless, this proof-of-principle study demonstrates the potential applicability of integration of these advanced analytical platforms to improve discrimination between colorectal cancer cases and controls based on metabolite profiles in future studies.
Highlights
Untargeted metabolomics has been increasingly employed in the past decade for biomarker discoveries for various diseases/conditions as well as for metabolome-wide association studies [1,2].This is expected to lead to a mechanistic understanding of diseases and applications of precision medicine and personalized intervention
To further increase metabolite coverage and achieve high accuracy of metabolite quantification, we have developed a method by analyzing the same metabolite sample on comprehensive two-dimensional gas chromatography-mass spectrometry (GC × GC-MS) and two-dimensional liquid chromatography-mass spectrometry (2DLC-MS)
Our two-dimensional gas chromatography was configured in comprehensive mode, i.e., multiple fractions are collected from the first-dimension column with a modulation period of 2.00 s and each fraction was subjected to the second-dimension column for further separation
Summary
Untargeted metabolomics has been increasingly employed in the past decade for biomarker discoveries for various diseases/conditions as well as for metabolome-wide association studies [1,2]. This is expected to lead to a mechanistic understanding of diseases and applications of precision medicine and personalized intervention. Comparing with NMR, GC-MS and LC-MS are more sensitive and provide much-increased metabolite coverage. Each of these two methods still has limited resolving power for analysis of complex samples such as metabolites in a biological sample, and none of them is able to analyze all metabolites.
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