title: Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment.
abstract: Lung cancer causes more deaths in men and women than any other cancer related disease. Currently, few effective strategies exist to predict how patients will respond to treatment. We evaluated the serum metabolomic profiles of 25 lung cancer patients undergoing chemotherapy ± radiation to evaluate the feasibility of metabolites as temporal biomarkers of clinical outcomes. Serial serum specimens collected prospectively from lung cancer patients were analyzed using both nuclear magnetic resonance (1H-NMR) spectroscopy and gas chromatography mass spectrometry (GC-MS). Multivariate statistical analysis consisted of unsupervised principal component analysis or orthogonal partial least squares discriminant analysis with significance assessed using a cross-validated ANOVA. The metabolite profiles were reflective of the temporal distinction between patient samples before during and after receiving therapy (1H-NMR, p < 0.001: and GC-MS p < 0.01). Disease progression and survival were strongly correlative with the GC-MS metabolite data whereas stage and cancer type were associated with1H-NMR data. Metabolites such as hydroxylamine, tridecan-1-ol, octadecan-1-ol, were indicative of survival (GC-MS p < 0.05) and metabolites such as tagatose, hydroxylamine, glucopyranose, and threonine that were reflective of progression (GC-MS p < 0.05). Metabolite profiles have the potential to act as prognostic markers of clinical outcomes for lung cancer patients. Serial1H-NMR measurements appear to detect metabolites diagnostic of tumor pathology, while GC-MS provided data better related to prognostic clinical outcomes, possibility due to physiochemical bias related to specific biochemical pathways. These results warrant further study in a larger cohort and with various treatment options.
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre and Cumming School of Medicine, University of Calgary, 1331-29th Street N.W., Calgary, AB T2N 4N2 Canada.
authors.forename: Desirée
authors.initials: D
authors.lastname: Hao
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4 Canada.|Department of Medicine-Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8N 3Z5 Canada.
authors.forename: M Omair
authors.initials: MO
authors.lastname: Sarfaraz
authors.affiliation: Department of Medical Oncology, Cumming School of Medicine, University of Calgary, 1331-29th Street N.W., Calgary, AB T2N 4N2 Canada.
authors.forename: Farshad
authors.initials: F
authors.lastname: Farshidfar
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre and Cumming School of Medicine, University of Calgary, 1331-29th Street N.W., Calgary, AB T2N 4N2 Canada.
authors.forename: D Gwyn
authors.initials: DG
authors.lastname: Bebb
authors.affiliation: Tom Baker Cancer Centre, 1331-29th Street N.W., Calgary, AB T2N 4N2 Canada.
authors.forename: Camelia Y
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre and Cumming School of Medicine, University of Calgary, 1331-29th Street N.W., Calgary, AB T2N 4N2 Canada.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Card
authors.affiliation: Clinical Research Unit, Tom Baker Cancer Centre, 1331-29th Street N.W., Calgary, AB T2N 4N2 Canada.
authors.forename: Marilyn
authors.initials: M
authors.lastname: David
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4 Canada.|Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104 USA.|Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
authors.forename: Aalim M
authors.identifier: 0000-0002-7145-4494
authors.initials: AM
authors.lastname: Weljie
keywords: GC–MS; Lung cancer; Metabolomics; NMR; Personalized medicine; Pharmacometabolomics