Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.
Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.
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DOI：
10.1016/j.bbmt.2015.07.004
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Paczesny S
中科院分区：
文献类型：
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作者：
Akil A;Zhang Q;Mumaw CL;Raiker N;Yu J;Velez de Mendizabal N;Haneline LS;Robertson KA;Skiles J;Diaz-Ricart M;Carreras E;Renbarger J;Hanash S;Bies RR;Paczesny S
造血细胞移植（HCT）后早期诊断和治疗窦阻塞综合征（SOS）需要可靠的，非侵入性的方法。我们使用定量质谱为基础的蛋白质组学方法，通过比较20例患者和20例无SOS患者的血浆，确定SOS的候选生物标志物。在定量的494种蛋白质中，我们选择了6种蛋白质[L-Ficolin、血管细胞粘附分子-1（VCAM 1）、金属蛋白酶组织抑制剂-1（tissue-inhibitor of metalloproteinase-1）、血管性血友病因子（von Willebrand factor）、细胞间粘附分子-1（intercellular-adhesion-molecule-1）和CD 97]，这是基于至少2倍的不同重/轻同位素比、文献信息和免疫测定可用性。接下来，我们评估了这六种蛋白质和从文献中选择的五种蛋白质[抑制致瘤性-2（ST 2）、血管生成素-2（ANG 2）、透明质酸（HA）、血栓调节蛋白和纤溶酶原激活物抑制剂-1]在80例患者样本中的诊断潜力。结果表明，ST 2、ANG 2、L-Ficolin、HA和VCAM 1一起构成了用于诊断SOS的生物标志物组。L-Ficolin、HA和VCAM 1也早在HCT当天就对存在SOS风险的患者进行了分层。基于HCT当天的L-Ficolin、HA和VCAM 1水平和临床特征的SOS发作的预后贝叶斯建模显示SOS发作的正确预后>80%。这些生物标志物可提供预先干预的机会，以最大限度地减少SOS的发生率和/或严重程度。
Reliable, non-invasive 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 six 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 six proteins and five 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.