A Comprehensive Workflow of Mass Spectrometry-Based Untargeted Metabolomics in Cancer Metabolic Biomarker Discovery Using Human Plasma and Urine

Metabolites. 2013;3(3):787-819 DOI 10.3390/metabo3030787


Journal Homepage

Journal Title: Metabolites

ISSN: 2218-1989 (Print)

Publisher: MDPI AG

LCC Subject Category: Science: Microbiology

Country of publisher: Switzerland

Language of fulltext: English

Full-text formats available: PDF, HTML



Jianwen She
Wei Zou
Vladimir V. Tolstikov


Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 11 weeks


Abstract | Full Text

Current available biomarkers lack sensitivity and/or specificity for early detection of cancer. To address this challenge, a robust and complete workflow for metabolic profiling and data mining is described in details. Three independent and complementary analytical techniques for metabolic profiling are applied: hydrophilic interaction liquid chromatography (HILIC–LC), reversed-phase liquid chromatography (RP–LC), and gas chromatography (GC). All three techniques are coupled to a mass spectrometer (MS) in the full scan acquisition mode, and both unsupervised and supervised methods are used for data mining. The univariate and multivariate feature selection are used to determine subsets of potentially discriminative predictors. These predictors are further identified by obtaining accurate masses and isotopic ratios using selected ion monitoring (SIM) and data-dependent MS/MS and/or accurate mass MSn ion tree scans utilizing high resolution MS. A list combining all of the identified potential biomarkers generated from different platforms and algorithms is used for pathway analysis. Such a workflow combining comprehensive metabolic profiling and advanced data mining techniques may provide a powerful approach for metabolic pathway analysis and biomarker discovery in cancer research. Two case studies with previous published data are adapted and included in the context to elucidate the application of the workflow.