title: Serum proteomics in multiple sclerosis disease progression.
abstract: Multiple sclerosis (MS) is associated with chronic degeneration of the central nervous system and may cause permanent neurological problems and considerable disability. While its causes remain unclear, its extensive phenotypic variability makes its prognosis and treatment difficult. The identification of serum proteomic biomarkers of MS progression could further our understanding of the molecular mechanisms related to MS disease processes. In the current study, we used isobaric tagging for relative and absolute protein quantification (iTRAQ) methodology and advanced multivariate statistical analysis to quantify and identify potential serum biomarker proteins of MS progression. We identified a panel of 11 proteins and combined them into a classifier that best classified samples into the two disease groups. The estimated area under the receiver operating curve of this classifier was 0.88 (p-value=0.017), with 86% sensitivity and specificity. The identified proteins encompassed processes related to inflammation, opsonization, and complement activation. Results from this study are in particular valuable to design a targeted Multiple Reaction Monitoring mass spectrometry based (MRM-MS) assay to conduct an external validation in an independent and larger cohort of patients. Validated biomarkers may result in the development of a minimally-invasive tool to monitor MS progression and complement current clinical practices.
  
  
  CONCLUSIONS
  A hallmark of multiple sclerosis is the unpredictable disease course (progression). There are currently no clinically useful biomarkers of MS disease progression; most work has focused on the analysis of CSF, which requires an invasive procedure. Here, we explore the potential of proteomics to identify panels of serum biomarkers of disease progression in MS. By comparing the protein signatures of two challenging to obtain, but well-defined, MS phenotypic groups at the extremes of progression (benign and aggressive cases of MS), we identified proteins that encompass processes related to inflammation, opsonization, and complement activation. Findings require validation, but are an important step on the pathway to clinically useful biomarker discovery. This article is part of a Special Issue entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault and Anne-Claude Gingras.
authors.affiliation: Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
authors.affiliation: PROOF Centre of Excellence, Vancouver, BC V6Z 1Y6, Canada; Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Darlene L Y
authors.initials: DL
authors.lastname: Dai
authors.affiliation: PROOF Centre of Excellence, Vancouver, BC V6Z 1Y6, Canada.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.affiliation: Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Kapanen
authors.affiliation: Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
authors.forename: Tariq
authors.initials: T
authors.lastname: Aziz
authors.affiliation: PROOF Centre of Excellence, Vancouver, BC V6Z 1Y6, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Wilson-McManus
authors.affiliation: Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada; PROOF Centre of Excellence, Vancouver, BC V6Z 1Y6, Canada; Department of Medicine, Division of Respiratory Medicine, Canada.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Tebbutt
authors.affiliation: University of Victoria Genome BC Proteomics Centre, Victoria, BC V8Z 7X8, Canada.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
authors.affiliation: Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Oger
authors.affiliation: PROOF Centre of Excellence, Vancouver, BC V6Z 1Y6, Canada; Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: gcohen@stat.ubc.ca.
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Cohen Freue
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome
keywords: Biomarkers; Classifier; MS progression; Multiple sclerosis; Serum proteomics; iTRAQ mass spectrometry