Article ID Journal Published Year Pages File Type
2101312 Biology of Blood and Marrow Transplantation 2015 7 Pages PDF
Abstract

•Suppression of tumorigenicity-2, angiopoietin-2, L-Ficolin, hyaluronic acid, and vascular cell adhesion molecule-1 represent a biomarker panel for sinusoidal obstruction syndrome diagnosis•L-Ficolin, hyaluronic acid, and vascular cell adhesion molecule-1 are prognostic biomarkers of sinusoidal obstruction syndrome before symptoms appear•These biomarkers can stratify patients at risk for sinusoidal obstruction syndrome as early as the day of hematopoietic cell transplantation•L-Ficolin has a mechanism of action unrelated to hemostasis and endothelial injury

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.

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