title: Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation.
abstract: Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS.
authors.affiliation: Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN.
authors.forename: Z
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN.|Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN.|Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN.|Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN.|Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: E
authors.initials: E
authors.lastname: Daguindau
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN.|Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN.|Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: K
authors.initials: K
authors.lastname: Kushekhar
authors.affiliation: Proteomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Proteomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Proteomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: P R
authors.initials: PR
authors.lastname: Gafken
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.|Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Pulmonary Division, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: A
authors.initials: A
authors.lastname: Gracon
authors.affiliation: Pulmonary Division, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: D S
authors.initials: DS
authors.lastname: Wilkes
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.|University of Washington School of Medicine, Seattle, WA.
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.|University of Washington School of Medicine, Seattle, WA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN.
authors.forename: J Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN.|Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN.|Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: S
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001989:Bronchiolitis Obliterans / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020543:Proteome; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: basic (laboratory) research/science; biomarker; bone marrow/hematopoietic stem cell transplantation; bronchiolitis obliterans (BOS); lung transplantation/pulmonology; translational research/science