Plasma gelsolin protein: a candidate biomarker for hepatitis B-associated liver cirrhosis identified by proteomic approach
Plasma gelsolin protein: a candidate biomarker for hepatitis B-associated liver cirrhosis identified by proteomic approach
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DOI：
10.2450/2010.017s
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发表时间：
2010-06-01
影响因子：
3.7
通讯作者：
Zolla, Lello
中科院分区：
文献类型：
--
作者：
Marrocco, Cristina;Rinalducci, Sara;Zolla, Lello
背景尽管近年来内科和支持性治疗有了显著改善，但肝纤维化/肝硬化仍然是B型肝炎病毒（HBV）感染患者的严重健康问题。侵入性肝活检是目前诊断肝硬化的最佳手段，但它具有显著的风险，并且具有公认的局限性，例如采样误差，因此开发早期诊断生物标志物的重要性。为此，我们进行了一项初步的蛋白质组学研究，以评估其作为HBV相关性肝硬化患者血浆标志物检测的策略。从8例慢性HBV感染患者和8例HBV相关性腹泻患者中选择血浆，并通过双向电泳建立蛋白质组图谱。该策略包括在蛋白质组学分析之前使用ProteoMiner富集试剂盒减少高丰度蛋白质（例如白蛋白和IgG），目的是提高新候选标记物的检测。一个可重复的斑点被发现是完全压抑的血浆样品中从阿尔茨海默病患者和质谱分析确定这是一个特定的凝溶胶蛋白肌动蛋白解聚因子的变体。虽然需要进一步的研究，特别是在临床验证方面，但据我们所知，这是首次提出凝溶胶蛋白作为HBV相关肝脏病理学的潜在生物标志物。我们的研究结果证实了凝溶胶蛋白作为预后标志物或替代治疗剂以减轻肝损伤的潜在效用。
Background. Despite the significant improvement in internal medicine and supportive therapy in recent years, liver fibrosis/cirrhosis remains a serious health issue in hepatitis B virus (HBV) infected patients. Invasive liver biopsy is presently the best means of diagnosing cirrhosis, but it carries a significant risk and has well recognised limitations such as sampling error, hence the importance in developing early diagnosis biomarkers. With this aim, we performed a pilot proteomic study to assess this as a strategy for plasma marker detection in patients suffering from HBV-associated liver cirrhosis.Methods. Plasma from eight chronic HBV-infection patients and from eight HBV-related cirrhotic patients were selected and proteome profiles were created by two-dimensional electrophoresis. The strategy included the use of ProteoMiner enrichment kit for the reduction of highly abundance proteins (e.g. albumin and IgG) prior to proteomic analyses with the goal to improve detection of novel candidate markers.Results. One reproducible spot was found to be completely repressed in plasma samples from cirrhotic patients and mass spectrometry analysis identified this a specific variant of the gelsolin actin-depolymerizing factor. Though further investigations are needed, especially in term of clinical validation, to our knowledge this is the first time that gelsolin is proposed as potential biomarker in HBV-related liver pathologies.Conclusions. Our findings confirm the potential utility of gelsolin either as a prognostic marker or a replacement therapeutic agent to alleviate liver injury.