The discovery and identification of a candidate proteomic biomarker of active tuberculosis.

The discovery and identification of a candidate proteomic biomarker of active tuberculosis.
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活动性结核病候选蛋白质组生物标志物的发现和鉴定

DOI:
10.1186/1471-2334-13-506
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发表时间:
2013-10-29
影响因子:
3.7
通讯作者:
Li JC
Li JC
中科院分区:
医学3区
文献类型:
--
作者:
Liu J;Jiang T;Wei L;Yang X;Wang C;Zhang X;Xu D;Chen Z;Yang F;Li JC

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背景:用于结核病早期诊断的非侵入性和方便的生物标志物仍然是迫切需要的。方法采用表面增强激光解吸电离飞行时间质谱仪(SELDI-TOF MS)结合弱阳离子交换磁珠(WCX)对180例TB患者和211例正常对照的血清标本进行筛查。应用Biomarker Pattern Software(BPS)建立分类模型。结果共检测到35个与结核病相关的m/z峰(P< 0.01)。建立了以2554.6、4824.4、5325.7、8606.8等4个生物标记物为基础的生物标记物模型,其敏感性为83.3%,特异度为84.2%。M/z为2554.6 Da的候选生物标志物在结核病患者中表达上调,并被鉴定为纤维蛋白原、α多肽亚型α-E前蛋白的一个片段。22例肺结核患者血浆纤维蛋白原降解产物升高(5,005 ± 1,297vs.4,010 ± 1,181 ng/mL,P< 0.05),142例患者血浆纤维蛋白原水平升高。纤维蛋白原被认为是一种潜在的结核病生物标志物,具有临床诊断价值。
BackgroundNoninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB.MethodsThe surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA).ResultsA total of 35 discriminating m/z peaks were detected that were related to TB (P< 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL,P< 0.05) and in 142 patients showed elevated plasma fibrinogen levels.ConclusionsA diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.
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发表时间: 2010-01-01
期刊: ACTA HISTOCHEMICA
影响因子: 2.5
作者:
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