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. 2015 Oct;21(10):1739-45.
doi: 10.1016/j.bbmt.2015.07.004. Epub 2015 Jul 11.

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

Ayman Akil  1 , Qing Zhang  2 , Christen L Mumaw  3 , Nisha Raiker  3 , Jeffrey Yu  3 , Nieves Velez de Mendizabal  1 , Laura S Haneline  4 , Kent A Robertson  5 , Jodi Skiles  5 , Maribel Diaz-Ricart  6 , Enric Carreras  7 , Jamie Renbarger  8 , Samir Hanash  9 , Robert R Bies  1 , Sophie Paczesny  10
Affiliations

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

Ayman Akil et al. Biol Blood Marrow Transplant. 2015 Oct.

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; SOS; Sinusoidal obstruction syndrome; VOD; Veno-occlusive disease.

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Figures

Figure 1
Figure 1. Diagnostic biomarkers of SOS according to the highest AUCs (0.91–0.70) in the training cohort
Plasma biomarker concentrations measured by ELISA in patients with SOS (SOS+) and without SOS (SOS−) (A–H). The data are shown as mean ± standard error of the mean (SEM). Unpaired t test, significant at p < 0.05. The numbers beneath the SOS categories are the AUC percentages for each marker.
Figure 2
Figure 2. Prognostic biomarkers of SOS prior the clinical signs in the training cohort
Plasma biomarker concentrations measured by ELISA in patients with SOS (SOS+) and without SOS (SOS−) at different days post-HCT (0, +7, +14). The data are shown as mean ± standard error of the mean (SEM). Median differences assessed with Wilcoxon rank sum test, significant at p < 0.05. The numbers beneath the SOS categories are the AUC percentages for each marker and days post-HCT when significant.
Figure 3
Figure 3. Prognostic biomarkers prior the clinical signs of SOS in the independent cohort
Plasma biomarker concentrations measured by ELISA in patients with SOS (SOS+) and without SOS (SOS−) at different days post-HCT (−7, 0, +7, +14). The data are shown as mean ± standard error of the mean (SEM). Median differences assessed with Wilcoxon rank sum test, significant at p < 0.05. The numbers beneath the SOS categories are the AUC percentages for each marker and days post-HCT when significant.
See this image and copyright information in PMC

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