Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome
Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome
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DOI：
10.1002/elps.201200002
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发表时间：
2012-07-01
期刊：
影响因子：
2.9
通讯作者：
Lo, Y. M. Dennis
中科院分区：
文献类型：
--
作者：
Poon, Terence C. W.;Pang, Ronald T. K.;Lo, Y. M. Dennis
此前，我们报道了严重急性呼吸综合征（SARS）患者血清中存在蛋白质组指纹，并且可以将患者分为具有不同预后的亚组。在本研究中，我们通过生物统计分析检查了 SARS 相关蛋白质组学特征的预后价值，并破译了具有预后价值的个体的身份。对 38 名 SARS 成年患者治疗前的 20 种 SARS 相关血清蛋白质组特征和 10 种血清学变量的数据进行多变量逻辑回归。 m/z 6634、m/z 7769、m/z 8635 和 m/z 8865 的蛋白质组学特征被确定为独立的预后标志物。经阳离子交换层析和凝胶电泳纯化后，串联质谱检测m/z 7769和m/z 8865的蛋白质组学特征分别为血小板因子4（PF4）和β-血栓球蛋白（β-TG）。 Western blot 证实了血清 PF4 降低和血清 β-TG 水平升高与不良预后的关联。先前的研究表明PF4和β-TG分别以消极和积极的方式参与急性呼吸窘迫综合征（ARDS）的发病机制。我们的结果表明，PF4 和 beta-TG 也可能在 SARS 患者发生 ARDS 的过程中发挥类似的作用。
Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS-associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS-associated serum proteomic features and ten serological variables from 38 SARS adult patients before treatment were subjected to multivariate logistic regression. Proteomic features of m/z 6634, m/z 7769, m/z 8635, and m/z 8865 were identified as independent prognostic markers. After purification by cation-exchange chromatography and gel electrophoresis, proteomic features of m/z 7769 and m/z 8865 were found to be platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) by tandem mass spectrometry, respectively. The associations of decreased serum PF4 and increased serum beta-TG levels with poor prognosis were confirmed by Western blot. Previous studies suggest that PF4 and beta-TG are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) in a negative and positive way, respectively. Our results suggest that PF4 and beta-TG may also play similar roles in the development of ARDS in SARS patients.