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 S.
AU - Robertson, Kent A.
AU - Skiles, Jodi
AU - Diaz-Ricart, Maribel
AU - Carreras, Enric
AU - Renbarger, Jamie
AU - Hanash, Samir
AU - Bies, Robert R.
AU - Paczesny, Sophie
N1 - Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.
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 - SOS
KW - Sinusoidal obstruction syndrome
KW - VOD
KW - Veno-occlusive disease
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U2 - 10.1016/j.bbmt.2015.07.004
DO - 10.1016/j.bbmt.2015.07.004
M3 - Article
C2 - 26172478
AN - SCOPUS:84941274069
SN - 1083-8791
VL - 21
SP - 1739
EP - 1745
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -