title: Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury.
abstract: Suffering an acute spinal cord injury (SCI) can result in catastrophic physical and emotional loss. Efforts to translate novel therapies in acute clinical trials are impeded by the SCI community's singular dependence upon functional outcome measures. Therefore, a compelling rationale exists to establish neurochemical biomarkers for the objective classification of injury severity. In this study, CSF and serum samples were obtained at 3 time points (~24, 48, and 72 hours post-injury) from 30 acute SCI patients (10 AIS A, 12 AIS B, and 8 AIS C). A differential chemical isotope labeling liquid chromatography mass spectrometry (CIL LC-MS) with a universal metabolome standard (UMS) was applied to the metabolomic profiling of these samples. This method provided enhanced detection of the amine- and phenol-containing submetabolome. Metabolic pathway analysis revealed dysregulations in arginine-proline metabolism following SCI. Six CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC > 0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients. Using the UMS strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, AB, T6G2G2, Canada.
authors.forename: Yiman
authors.initials: Y
authors.lastname: Wu
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Femke
authors.initials: F
authors.lastname: Streijger
authors.affiliation: Department of Computing Science, University of Alberta, Edmonton, AB, T6T 2E8, Canada.
authors.forename: Yining
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Computing Science, University of Alberta, Edmonton, AB, T6T 2E8, Canada.
authors.forename: Guohui
authors.initials: G
authors.lastname: Lin
authors.affiliation: Division of Neurosurgery, Dalhousie University, Halifax Infirmary, 1796 Summer Street, Halifax, NS, B3H 3A7, Canada.
authors.forename: Sean
authors.initials: S
authors.lastname: Christie
authors.affiliation: Hôpital du Sacré-Coeur de Montréal, 5400 Boul Gouin O, Montréal, QC, H4J 1C5, Canada.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Mac-Thiong
authors.affiliation: Chu Sainte-Justine, Dept. of Surgery, Université de Montréal, PO Box 6128, Station Centre-ville, Montreal, QC, H3C 3J7, Canada.
authors.forename: Stefan
authors.initials: S
authors.lastname: Parent
authors.affiliation: Division of Orthopaedic Surgery, Schulich Medicine &Dentistry, Victoria Hospital 800 Commissioners Road East, Room E4 120, London, ON, N6C 5W9, Canada.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Bailey
authors.affiliation: Division of Neurosurgery, University of British Columbia, Vancouver Spine Surgery Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Paquette
authors.affiliation: Division of Neurosurgery, University of British Columbia, Vancouver Spine Surgery Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Boyd
authors.affiliation: Division of Neurosurgery, University of British Columbia, Vancouver Spine Surgery Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Tamir
authors.initials: T
authors.lastname: Ailon
authors.affiliation: Department of Orthopaedics, University of British Columbia, Vancouver Spine Surgery Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Street
authors.affiliation: Department of Orthopaedics, University of British Columbia, Vancouver Spine Surgery Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Fisher
authors.affiliation: Department of Orthopaedics, University of British Columbia, Vancouver Spine Surgery Institute, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Dvorak
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kwon
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, AB, T6G2G2, Canada.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers