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- Title
A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.
- Authors
Farshidfar, Farshad; Weljie, Aalim M; Kopciuk, Karen A; Hilsden, Robert; McGregor, S Elizabeth; Buie, W Donald; MacLean, Anthony; Vogel, Hans J; Bathe, Oliver F
- Abstract
<bold>Background: </bold>Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood-based biomarker series using a single assay, suitable for CRC detection, prognostication and staging.<bold>Methods: </bold>Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS-DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated.<bold>Results: </bold>A diagnostic signature for CRC with remarkable multivariate performance (R(2)Y=0.46, Q(2)Y=0.39) was constructed, and then validated (sensitivity 85%; specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87-0.96). Adenomas were also detectable (R(2)Y=0.35, Q(2)Y=0.26, internal AUROC=0.81, 95% CI, 0.70-0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage.<bold>Conclusions: </bold>Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers.
- Publication
British Journal of Cancer, 2016, Vol 115, Issue 7, p848
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2016.243