Serum protein S100A9, SOD3, and MMP9 as new diagnostic biomarkers for pulmonary tuberculosis by iTRAQ-coupled two-dimensional LC-MS/MS
Serum protein S100A9, SOD3, and MMP9 as new diagnostic biomarkers for pulmonary tuberculosis by iTRAQ-coupled two-dimensional LC-MS/MS
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DOI：
10.1002/pmic.201400366
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发表时间：
2015-01-01
期刊：
影响因子：
3.4
通讯作者：
Li, Ji-Cheng
中科院分区：
文献类型：
--
作者：
Xu, Dandan;Li, Yanyuan;Li, Ji-Cheng
本研究旨在寻找新的无创性诊断肺结核的生物标志物。我们应用iTRAQ 2D LC-MS/MS技术研究肺结核和其他肺部疾病患者的蛋白质谱。在肺结核患者血清中共鉴定出34个差异表达蛋白（24个上调蛋白和10个下调蛋白）。ELISA法检测肺结核与其他肺部疾病患者血清中S100-A9（S100 A9）、细胞外超氧化物歧化酶[Cu-Zn]（SOD 3）和基质金属蛋白酶9（MMP 9）的含量差异有统计学意义。相关分析显示，肺结核患者血清MMP 9水平与SOD 3（r = 0.581）、S100 A9（r = 0.471）呈中度相关，而SOD 3与S100 A9呈弱相关（r = 0.287）。血清S100 A9、SOD 3和MMP 9水平的组合可以分别达到区分肺结核和健康对照的92.5%灵敏度和95%特异性，区分肺结核和肺炎的90%灵敏度和87.5%特异性，以及区分肺结核和肺癌的85%灵敏度和92.5%特异性。结果表明，S100 A9、SOD 3和MMP 9可能是肺结核潜在的诊断标志物，为肺结核的诊断提供了实验依据。
This study aimed to discover the novel noninvasive biomarkers for the diagnosis of pulmonary tuberculosis (TB). We applied iTRAQ 2D LC-MS/MS technique to investigate protein profiles in patients with pulmonary TB and other lung diseases. A total of 34 differentially expressed proteins (24 upregulated proteins and ten downregulated proteins) were identified in the serum of pulmonary TB patients. Significant differences in protein S100-A9 (S100A9), extracellular superoxide dismutase [Cu-Zn] (SOD3), and matrix metalloproteinase 9 (MMP9) were found between pulmonary TB and other lung diseases by ELISA. Correlations analysis revealed that the serum concentration of MMP9 in the pulmonary TB was in moderate correlation with SOD3 (r = 0.581) and S100A9 (r = 0.471), while SOD3 was in weak correlation with S100A9 (r = 0.287). The combination of serum S100A9, SOD3, and MMP9 levels could achieve 92.5% sensitivity and 95% specificity to discriminate between pulmonary TB and healthy controls, 90% sensitivity and 87.5% specificity to discriminate between pulmonary TB and pneumonia, and 85% sensitivity and 92.5% specificity to discriminate between pulmonary TB and lung cancer, respectively. The results showed that S100A9, SOD3, and MMP9 may be potential diagnostic biomarkers for pulmonary TB, and provided experimental basis for the diagnosis of pulmonary TB.