title: Biomarker discovery for inflammatory bowel disease, using proteomic serum profiling.
abstract: Crohn's disease and ulcerative colitis known as inflammatory bowel diseases (IBD) are chronic immuno-inflammatory pathologies of the gastrointestinal tract. These diseases are multifactorial, polygenic and of unknown etiology. Clinical presentation is non-specific and diagnosis is based on clinical, endoscopic, radiological and histological criteria. Novel markers are needed to improve early diagnosis and classification of these pathologies. We performed a study with 120 serum samples collected from patients classified in 4 groups (30 Crohn, 30 ulcerative colitis, 30 inflammatory controls and 30 healthy controls) according to accredited criteria. We compared protein sera profiles obtained with a Surface Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometer (SELDI-TOF-MS). Data analysis with univariate process and a multivariate statistical method based on multiple decision trees algorithms allowed us to select some potential biomarkers. Four of them were identified by mass spectrometry and antibody based methods. Multivariate analysis generated models that could classify samples with good sensitivity and specificity (minimum 80%) discriminating groups of patients. This analysis was used as a tool to classify peaks according to differences in level on spectra through the four categories of patients. Four biomarkers showing important diagnostic value were purified, identified (PF4, MRP8, FIBA and Hpalpha2) and two of these: PF4 and Hpalpha2 were detected in sera by classical methods. SELDI-TOF-MS technology and use of the multiple decision trees method led to protein biomarker patterns analysis and allowed the selection of potential individual biomarkers. Their downstream identification may reveal to be helpful for IBD classification and etiology understanding.
authors.affiliation: Laboratory of Clinical Chemistry, GIGA Research, CHU, University of Liège, B34, 4000 Liège, Belgium.
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Meuwis
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
authors.forename: Pierre
authors.initials: P
authors.lastname: Geurts
authors.forename: Dominique
authors.initials: D
authors.lastname: de Seny
authors.forename: Laurence
authors.initials: L
authors.lastname: Lutteri
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chapelle
authors.forename: Vincent
authors.initials: V
authors.lastname: Bours
authors.forename: Louis
authors.initials: L
authors.lastname: Wehenkel
authors.forename: Jacques
authors.initials: J
authors.lastname: Belaiche
authors.forename: Michel
authors.initials: M
authors.lastname: Malaise
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Merville
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis* / Q000503:physiopathology; D025202:Molecular Diagnostic Techniques; D053495:Osteopontin / Q000032:analysis; D010978:Platelet Factor 4 / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D053495:Osteopontin; D010978:Platelet Factor 4