Identification of novel protein biomarkers of preterm birth in human cervical-vaginal fluid

Identification of novel protein biomarkers of preterm birth in human cervical-vaginal fluid
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DOI:
10.1021/pr0605421
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发表时间:
2007-01-01
影响因子:
4.4
通讯作者:
Nagalla, Srinivasa R.
Nagalla, Srinivasa R.
中科院分区:
生物学2区
文献类型:
--
作者:
Pereira, Leonardo;Reddy, Ashok P.;Nagalla, Srinivasa R.

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自发性早产是围产儿发病率和死亡率的主要因素。然而,导致早产的早产(PTL)的诊断是困难的,迫切需要改进诊断。我们利用多维液相色谱-串联质谱仪(LC/LC-MS/MS;MudPIT)和荧光双向差示凝胶内电泳法(2D-DGE)来鉴定PTL和SPTB的潜在生物标志物。泥坑分析在宫颈-阴道液(CVF)中鉴定出205种蛋白质,其中28种蛋白质在成对比较和累进比较中显示出显著差异。钙粒蛋白、膜联蛋白、S100钙结合蛋白A7和表皮脂肪酸结合蛋白在CVF中含量丰富,在PTL和SPTB中存在差异,血清蛋白α-1-抗胰蛋白酶、α1-酸性糖蛋白、结合珠蛋白、转铁蛋白和维生素D结合蛋白也是如此。2D-DGE鉴定出17种在PTL和SPTB中存在显著差异的蛋白质。用特异性抗体进行免疫印迹,证实了所选标记物的差异和趋势。在更大的受试者队列中进一步表征和量化这些标记物可能会为早期、非侵入性的SPTB阳性预测提供新的测试基础。
Spontaneous preterm birth (SPTB) is a major contributor to perinatal morbidity and mortality. However, the diagnosis of preterm labor (PTL) that leads to preterm birth is difficult, and there is a pressing need for improved diagnosis. We utilized multidimensional liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS; MudPIT) and Fluorescence two-dimensional differential in-gel electrophoresis (2D-DIGE) to identify potential biomarkers of PTL and SPTB. MudPIT analysis identified 205 proteins in cervical-vaginal fluid (CVF), 28 of which exhibited significant differences in pairwise and progressive comparisons. Calgranulins, annexins, S100 calcium-binding protein A7, and epidermal fatty acid binding protein were abundant in CVF and differentially present in PTL and SPTB samples, as were the serum proteins alpha-1-antitrypsin, alpha 1-acid glycoprotein, haptoglobin, serotransferrin, and vitamin D binding protein. 2D-DIGE identified 17 proteins that were significantly differentially present in PTL and SPTB. Immunoblotting with specific antibodies confirmed the differences and trends of selected markers. Further characterization and quantification of these markers in a larger cohort of subjects may provide the basis for new tests for the early, noninvasive positive prediction of SPTB.