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首页> 外文期刊>Journal of proteomics >Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth
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Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth

机译:孕孕孕期母体血清的蛋白质组学分析,以确定潜在预测自发早产的候选生物标志物

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Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder. Biological significance: Identifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare preterm ( 37 weeks) and preterm (= 37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a clinical setting as well as for future investigation of underlying aetiological processes.
机译:自发早产(SPTB)仍然是一个主要的临床困境;目前的诊断和干预措施并没有减少这种严重的医疗保健负担的速度。本研究表征了使用精制的自上而下方法耦合二维凝胶电泳(2DE)和质谱法(MS)以直接比较随后的术语和早产事件并鉴定标记的蛋白质差异。在包括9种磷蛋白蛋白和11种糖蛋白的SPTB基团中发现30个蛋白质常规显着增加或减少。与免疫和防御反应相关的蛋白质中发生的变化。我们鉴定了与几种临床相关的生物过程相关的蛋白质物种,包括与补体级联和凝血途径,免疫调节,代谢过程和细胞信号传导相关的相互关联的生物网络。从递送早产的孕妇血清中的改变的蛋白质ords的发现表明这些是SPTB的潜在早期生物标志物,也是疾病的可能介质。生物学意义:鉴定蛋白质谱的变化在细胞生物学研究中至关重要,疾病治疗和预防至关重要。在妊娠早期鉴定母体血清蛋白质组的一致变化,包括特异性蛋白质PTMS(例如磷酸化,糖基化),可能为预测,干预和预防早产提供更好的机会。这是第一次使用基于高分辨率2DE的高分辨率的自上而下的蛋白质组学分析方法来检查前妊娠期母体血清的第一项研究,与质​​谱相结合,直接比较早产(& 37周)和早产(& = 37周)事件并确定这些条件之间的选择蛋白质差异。因此,数据为临床环境的生物标志物发现的译文提供了一个有希望的途径,以及未来对潜在的安全性过程的调查。

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