title: Colorectal cancer detection using targeted serum metabolic profiling.
abstract: Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world. Despite an expanding knowledge of its molecular pathogenesis during the past two decades, robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC are still lacking. In this study, we present a targeted liquid chromatography-tandem mass spectrometry-based metabolic profiling approach for identifying biomarker candidates that could enable highly sensitive and specific CRC detection using human serum samples. In this targeted approach, 158 metabolites from 25 metabolic pathways of potential significance were monitored in 234 serum samples from three groups of patients (66 CRC patients, 76 polyp patients, and 92 healthy controls). Partial least-squares-discriminant analysis (PLS-DA) models were established, which proved to be powerful for distinguishing CRC patients from both healthy controls and polyp patients. Receiver operating characteristic curves generated based on these PLS-DA models showed high sensitivities (0.96 and 0.89, respectively, for differentiating CRC patients from healthy controls or polyp patients), good specificities (0.80 and 0.88), and excellent areas under the curve (0.93 and 0.95). Monte Carlo cross validation was also applied, demonstrating the robust diagnostic power of this metabolic profiling approach.
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Danijel
authors.initials: D
authors.lastname: Djukovic
authors.forename: Lingli
authors.initials: L
authors.lastname: Deng
authors.forename: Haiwei
authors.initials: H
authors.lastname: Gu
authors.forename: Farhan
authors.initials: F
authors.lastname: Himmati
authors.forename: E Gabriela
authors.initials: EG
authors.lastname: Chiorean
authors.forename: Daniel
authors.initials: D
authors.lastname: Raftery
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003111:Colonic Polyps / Q000097:blood / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015233:Models, Statistical; D012372:ROC Curve; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor