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蛋白质组学分析显示血小板因子 4 和β-血栓球蛋白是严重急性呼吸综合征的预后标志物。

Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome.

机构信息

Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR.

出版信息

Electrophoresis. 2012 Jul;33(12):1894-900. doi: 10.1002/elps.201200002.

Abstract

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.

摘要

先前,我们报道了在严重急性呼吸综合征(SARS)患者的血清中存在蛋白质组指纹,并可以将患者分为具有不同预后的亚组。在本研究中,我们通过生物统计学分析检查了 SARS 相关蛋白质组特征的预后价值,并破译了具有预后价值的特征。对 38 例 SARS 成人患者在治疗前的 20 个 SARS 相关血清蛋白质组特征和 10 个血清学变量的数据进行了多变量逻辑回归分析。鉴定出 m/z 6634、m/z 7769、m/z 8635 和 m/z 8865 的蛋白质组特征为独立的预后标志物。通过阳离子交换色谱和凝胶电泳纯化后,通过串联质谱法发现 m/z 7769 和 m/z 8865 的蛋白质组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 水平降低和血清β-TG 水平升高与预后不良的关联。先前的研究表明,PF4 和β-TG 分别以负向和正向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β-TG 也可能在 SARS 患者中 ARDS 的发展中发挥类似作用。

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