title: Non-invasive fecal metabonomic detection of colorectal cancer.
abstract: Colorectal cancer (CRC) is a major cause of mortality in many developed countries. Effective screening strategies were called for to facilitate timely detection and to promote a better clinical outcome. In this study, the role of fecal metabonomics in the non-invasive detection of CRC was investigated. Gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) was utilized for the metabolic profiling of feces obtained from 11 CRC patients and 10 healthy subjects. Concurrently, matched tumor and normal mucosae surgically excised from CRC patients were profiled. CRC patients were differentiated clearly from healthy subjects based on their fecal metabonomic profiles (orthogonal partial least squares discriminant analysis [OPLS-DA], 1 predictive and 3 Y-orthogonal components, R (2)X = 0.373, R (2)Y = 0.995, Q (2) [cumulative] = 0.215). The robustness of the OPLS-DA model was demonstrated by an area of 1 under the receiver operator characteristic curve. OPLS-DA revealed fecal marker metabolites (e.g., fructose, linoleic acid, and nicotinic acid) that provided novel insights into the tumorigenesis of CRC. Interestingly, a disparate set of CRC-related metabolic aberrations occurred at the tissue level, implying the contribution of processes beyond the direct shedding of tumor cells to the fecal metabotype. In summary, this work established proof-of-principle for GC/TOFMS-based fecal metabonomic detection of CRC and offered new perspectives on the underlying mechanisms.
authors.affiliation: Department of Pharmacy; Faculty of Science; National University of Singapore; Singapore.
authors.forename: Lee Cheng
authors.initials: LC
authors.lastname: Phua
authors.affiliation: Department of Pharmacy; Faculty of Science; National University of Singapore; Singapore.
authors.forename: Xiu Ping
authors.initials: XP
authors.lastname: Chue
authors.affiliation: Department of Colorectal Surgery; Singapore General Hospital; Singapore.
authors.forename: Poh Koon
authors.initials: PK
authors.lastname: Koh
authors.affiliation: Department of Colorectal Surgery; Singapore General Hospital; Singapore; Saw Swee Hock School of Public Health; National University of Singapore; Singapore; Duke-NUS Graduate Medical School; National University of Singapore; Singapore.
authors.forename: Peh Yean
authors.initials: PY
authors.lastname: Cheah
authors.affiliation: Department of Pharmacy; Faculty of Science; National University of Singapore; Singapore.
authors.forename: Han Kiat
authors.initials: HK
authors.lastname: Ho
authors.affiliation: Department of Pharmacy; Faculty of Science; National University of Singapore; Singapore.
authors.forename: Eric Chun Yong
authors.initials: EC
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor
keywords: colorectal cancer; feces; gas chromatography/time-of-flight mass spectrometry; metabolic profiling; metabolomics; metabonomics