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基于血浆蛋白质组学的儿童原发性免疫性血小板减少症诊断敏感标志物研究

Study on diagnostic-sensitive markers of primary immune thrombocytopenia in children based on plasma proteomics.

作者信息

Xu Wei, Wang Yun, Cao Qingqing, Xue Yuanyuan, Zhu Haiyan, Zhang Rongrong, Tian Zhaofang, Yuan Yufang

机构信息

Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

Department of Neonatology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

出版信息

Br J Haematol. 2024 Nov;205(5):1921-1929. doi: 10.1111/bjh.19730. Epub 2024 Aug 27.

Abstract

To use proteomic techniques to identify sensitive diagnostic biomarkers for paediatric immune thrombocytopenia (ITP). We selected children in ITP and control groups, using a four-dimensional data-independent acquisition approach (4D-DIA) to analyse its protein expression. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay (ELISA) validation in a cohort comprising 50 samples (13 healthy controls, 15 secondary thrombocytopenia controls and 22 children with ITP). Receiver operating characteristics (ROC) were generated to diagnose ITP and to assess the diagnostic effectiveness of this approach. Compared with the control group, 55 differentially expressed proteins (43 increased and 12 decreased) were determined in the ITP group. Matrix metalloproteinases-9 (MMP-9) and thrombospondin-1 (THBS1) were significantly expressed and selected for ELISA. The verification outcomes aligned with the findings from the proteomic examinations. In contrast to the control cohort, the ITP subjects exhibited markedly elevated plasma MMP-9 levels and reduced plasma THBS1 concentrations. Additionally, the ROC curves indicated the diagnostic value of these biomarkers. In conclusion, proteomics facilitates identifying the sensitive biomarkers for ITP diagnosis. We have preliminarily selected two differentially expressed proteins, MMP-9 and THBS1, whose potential role as biomarkers for diagnosing ITP requires further research.

摘要

利用蛋白质组学技术鉴定儿童免疫性血小板减少症(ITP)的敏感诊断生物标志物。我们选取了ITP组和对照组的儿童,采用四维数据非依赖采集方法(4D-DIA)分析其蛋白质表达。选择差异显著的蛋白质在一个包含50个样本(13名健康对照、15名继发性血小板减少症对照和22名ITP患儿)的队列中进行酶联免疫吸附测定(ELISA)验证。生成受试者操作特征(ROC)曲线以诊断ITP并评估该方法的诊断效能。与对照组相比,ITP组确定了55种差异表达蛋白(43种上调和12种下调)。基质金属蛋白酶-9(MMP-9)和血小板反应蛋白-1(THBS1)表达显著并被选用于ELISA。验证结果与蛋白质组学检测结果一致。与对照队列相比,ITP受试者血浆MMP-9水平显著升高,血浆THBS1浓度降低。此外,ROC曲线表明了这些生物标志物的诊断价值。总之,蛋白质组学有助于鉴定ITP诊断的敏感生物标志物。我们初步筛选出两种差异表达蛋白,MMP-9和THBS1,其作为ITP诊断生物标志物的潜在作用有待进一步研究。

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