title: Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.
abstract: Reliable, noninvasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected 6 proteins (L-Ficolin, vascular cell adhesion molecule-1 [VCAM1], tissue inhibitor of metalloproteinase-1, von Willebrand factor, intercellular adhesion molecule-1, and CD97) based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these 6 proteins and 5 selected from the literature (suppression of tumorigenicity-2 [ST2], angiopoietin-2 (ANG2), hyaluronic acid [HA], thrombomodulin, and plasminogen activator inhibitor-1) in samples from 80 patients. The results demonstrate that together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS. L-Ficolin, HA, and VCAM1 also stratified patients at risk for SOS as early as the day of HCT. Prognostic Bayesian modeling for SOS onset based on L-Ficolin, HA, and VCAM1 levels on the day of HCT and clinical characteristics showed >80% correct prognosis of SOS onset. These biomarkers may provide opportunities for preemptive intervention to minimize SOS incidence and/or severity.
authors.affiliation: Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Ayman
authors.initials: A
authors.lastname: Akil
authors.affiliation: Department of Genomics, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Christen L
authors.initials: CL
authors.lastname: Mumaw
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Nisha
authors.initials: N
authors.lastname: Raiker
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Nieves
authors.initials: N
authors.lastname: Velez de Mendizabal
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Haneline
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Kent A
authors.initials: KA
authors.lastname: Robertson
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jodi
authors.initials: J
authors.lastname: Skiles
authors.affiliation: Hospital Clinic, IDIBAPS, Barcelona, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Diaz-Ricart
authors.affiliation: Hospital Clinic, IDIBAPS, Barcelona, Spain; José Carreras Foundation & Leukemia Research Institute, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.affiliation: Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jamie
authors.initials: J
authors.lastname: Renbarger
authors.affiliation: Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
authors.affiliation: Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: sophpacz@iu.edu.
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D037102:Lectins / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D011379:Prognosis; D040901:Proteomics; D018570:Risk Assessment; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis; D000097604:Ficolins
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid; D018799:Intercellular Adhesion Molecule-1; D037102:Lectins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D000097604:Ficolins; C560822:TIMP1 protein, human
keywords: Biomarkers; Proteomics; SOS; Sinusoidal obstruction syndrome; VOD; Veno-occlusive disease