Serum amyloid A, protein Z, and C4b-binding protein β chain as new potential biomarkers for pulmonary tuberculosis.
Serum amyloid A, protein Z, and C4b-binding protein β chain as new potential biomarkers for pulmonary tuberculosis.
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血清淀粉样蛋白 A、蛋白 Z 和 C4b 结合蛋白 β 链作为肺结核新的潜在生物标志物
DOI：
10.1371/journal.pone.0173304
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li JC
中科院分区：
文献类型：
--
作者：
Jiang TT;Shi LY;Wei LL;Li X;Yang S;Wang C;Liu CM;Chen ZL;Tu HH;Li ZJ;Li JC
本研究的目的是寻找新的肺结核生物标志物。采用iTRAQ-二维液相色谱串联质谱联用技术筛选和鉴定结核病患者血清中差异表达的蛋白质。与健康对照组相比，结核病患者共发现79种异常蛋白质。其中，在肺结核或肺炎患者和慢性阻塞性肺疾病(COPD)患者之间观察到47个异常表达的蛋白有显著差异。肺结核患者血清淀粉样蛋白A、维生素K依赖蛋白Z和C4b结合蛋白β链水平均显著高于健康对照组(P<；0.0001)，但低于肺炎(n=72)和慢性阻塞性肺疾病(n=72)患者(P<；0.0001，P<；0.0001，P=0.0016)。治疗6个月后，72例肺结核患者治疗后SAA、ProZ水平显著升高(P=0.022，P<0.0001)，C4BPB水平显著下降(P=0.0038)。临床分析显示，肺结核患者的凝血指标和血脂指标与健康对照组、肺炎或慢性阻塞性肺病患者、治疗后的肺结核患者比较，差异有统计学意义(P<；0.05)。相关分析显示，肺结核病患者ProZ与INR(rS=0.414，P=0.044)、C4BPB与FIB(rS=0.617，P=0.0002)呈显著正相关。受试者工作特征曲线分析显示，SAA、ProZ、C4BPB联合诊断模型对肺结核病组与健康对照组、肺炎组、慢性阻塞性肺病组、治愈肺结核组的曲线下面积分别为0.972、0.928、0.957、0.969。综上所述，这些结果表明SAA、ProZ和C4BPB可能成为新的潜在的结核病生物标志物。我们的研究可能为结核病的鉴别诊断提供实验数据。
The aim of this study was to discover novel biomarkers for pulmonary tuberculosis (TB). Differentially expressed proteins in the serum of patients with TB were screened and identified by iTRAQ-two dimensional liquid chromatography tandem mass spectrometry analysis. A total of 79 abnormal proteins were discovered in patients with TB compared with healthy controls. Of these, significant differences were observed in 47 abnormally expressed proteins between patients with TB or pneumonia and chronic obstructive pulmonary disease (COPD). Patients with TB (n = 136) exhibited significantly higher levels of serum amyloid A (SAA), vitamin K-dependent protein Z (PROZ), and C4b-binding protein β chain (C4BPB) than those in healthy controls (n = 66) (P<0.0001 for each) albeit significantly lower levels compared with those in patients with pneumonia (n = 72) (P<0.0001 for each) or COPD (n = 72) (P<0.0001, P<0.0001, P = 0.0016, respectively). After 6 months of treatment, the levels of SAA and PROZ were significantly increased (P = 0.022, P<0.0001, respectively), whereas the level of C4BPB was significantly decreased (P = 0.0038) in treated TB cases (n = 72). Clinical analysis showed that there were significant differences in blood clotting and lipid indices in patients with TB compared with healthy controls, patients with pneumonia or COPD, and treated TB cases (P<0.05). Correlation analysis revealed significant correlations between PROZ and INR (rs = 0.414, P = 0.044), and between C4BPB and FIB (rs = 0.617, P = 0.0002) in patients with TB. Receiver operating characteristic curve analysis revealed that the area under the curve value of the diagnostic model combining SAA, PROZ, and C4BPB to discriminate the TB group from the healthy control, pneumonia, COPD, and cured TB groups was 0.972, 0.928, 0.957, and 0.969, respectively. Together, these results suggested that SAA, PROZ, and C4BPB may serve as new potential biomarkers for TB. Our study may thus provide experimental data for the differential diagnosis of TB.