Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Ayman Akil, Qing Zhang, Christen L. Mumaw, Nisha Raiker, Jeffrey Yu, Nieves Velez de Mendizabal, Laura Haneline, Kent Robertson, Jodi Skiles, Maribel Diaz-Ricart, Enric Carreras, Jamie Renbarger, Samir Hanash, Robert Bies, Sophie Paczesny

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1739-1745
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Hepatic Veno-Occlusive Disease
Cell Transplantation
Biomarkers
Vascular Cell Adhesion Molecule-1
Hyaluronic Acid
Angiopoietin-2
Thrombomodulin
Proteins
Tissue Inhibitor of Metalloproteinase-1
Plasminogen Activator Inhibitor 1
von Willebrand Factor
Intercellular Adhesion Molecule-1
Immunoassay
Isotopes
Proteomics
Mass Spectrometry

Keywords

  • Biomarkers
  • Proteomics
  • Sinusoidal obstruction syndrome
  • SOS
  • Veno-occlusive disease
  • VOD

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. / Akil, Ayman; Zhang, Qing; Mumaw, Christen L.; Raiker, Nisha; Yu, Jeffrey; Velez de Mendizabal, Nieves; Haneline, Laura; Robertson, Kent; Skiles, Jodi; Diaz-Ricart, Maribel; Carreras, Enric; Renbarger, Jamie; Hanash, Samir; Bies, Robert; Paczesny, Sophie.

In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 10, 01.10.2015, p. 1739-1745.

Research output: Contribution to journalArticle

Akil, Ayman ; Zhang, Qing ; Mumaw, Christen L. ; Raiker, Nisha ; Yu, Jeffrey ; Velez de Mendizabal, Nieves ; Haneline, Laura ; Robertson, Kent ; Skiles, Jodi ; Diaz-Ricart, Maribel ; Carreras, Enric ; Renbarger, Jamie ; Hanash, Samir ; Bies, Robert ; Paczesny, Sophie. / Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2015 ; Vol. 21, No. 10. pp. 1739-1745.
@article{b0fe09bf793e4381b0e1e2fa58ffa9c9,
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.",
keywords = "Biomarkers, Proteomics, Sinusoidal obstruction syndrome, SOS, Veno-occlusive disease, VOD",
author = "Ayman Akil and Qing Zhang and Mumaw, {Christen L.} and Nisha Raiker and Jeffrey Yu and {Velez de Mendizabal}, Nieves and Laura Haneline and Kent Robertson and Jodi Skiles and Maribel Diaz-Ricart and Enric Carreras and Jamie Renbarger and Samir Hanash and Robert Bies and Sophie Paczesny",
year = "2015",
month = "10",
day = "1",
doi = "10.1016/j.bbmt.2015.07.004",
language = "English",
volume = "21",
pages = "1739--1745",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

AU - Akil, Ayman

AU - Zhang, Qing

AU - Mumaw, Christen L.

AU - Raiker, Nisha

AU - Yu, Jeffrey

AU - Velez de Mendizabal, Nieves

AU - Haneline, Laura

AU - Robertson, Kent

AU - Skiles, Jodi

AU - Diaz-Ricart, Maribel

AU - Carreras, Enric

AU - Renbarger, Jamie

AU - Hanash, Samir

AU - Bies, Robert

AU - Paczesny, Sophie

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Proteomics

KW - Sinusoidal obstruction syndrome

KW - SOS

KW - Veno-occlusive disease

KW - VOD

UR - http://www.scopus.com/inward/record.url?scp=84941274069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941274069&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2015.07.004

DO - 10.1016/j.bbmt.2015.07.004

M3 - Article

C2 - 26172478

AN - SCOPUS:84941274069

VL - 21

SP - 1739

EP - 1745

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 10

ER -