Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.
Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.
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在败血症相关的miRNA靶基因编码的败血症患者中鉴定了四种新型血清蛋白生物标志物。
DOI：
10.1042/cs20130301
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Xie LX
中科院分区：
文献类型：
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作者：
Wang HJ;Wang BZ;Zhang PJ;Deng J;Zhao ZR;Zhang X;Xiao K;Feng D;Jia YH;Liu YN;Xie LX
本研究的目的是从我们先前在脓毒症患者中鉴定的六种血清miRNAs的靶基因中鉴定新的蛋白质生物标志物。通过生物信息学分析预测靶基因，ELISA检测脓毒症患者血清中相应蛋白的水平。ACVR 2A（activin A receptor，type IIA）、FOXO 1（forkhead box O 1）、IHH（Indian hedgehog）、STK 4（serine/threonine kinase 4）和DUSP 3（dual specificity phosphatase 3）被预测为6种miRNAs的靶基因，并将其编码的蛋白用于生物标志物鉴定。正常对照组、脓毒症组、严重脓毒症组和脓毒症休克组之间ACVR 2A（P<0.01）和FOXO 1（P<0.01）的表达差异均有统计学意义。此外，ACVR 2A（P=0.025）、FOXO 1（P<0.001）、IHH（P=0.001）和STK 4（P=0.001）的水平在存活者和非存活者中差异表达。DUSP 3水平在任何组之间均无显著差异。对4种差异表达蛋白的联合分析显示，预测概率的曲线下面积为0.875 [95%CI（置信区间）：0.785-0.965]，高于SOFA（序贯器官衰竭评估）和APACHE II（急性生理学和慢性健康评估II）评分。当预测概率值为0.449时，四种蛋白质的敏感性为68%，特异性为91%。ACVR 2A、FOXO 1和IHH水平的动态变化在所有时间点在存活者和非存活者之间显示差异表达。综合分析这4种蛋白对脓毒症患者28天死亡率的预测价值优于SOFA或APACHE II评分。在脓毒症患者中发现了四种由miRNA靶基因编码的新蛋白质生物标志物。4种蛋白联合分析对脓毒症预后的预测价值优于SOFA评分和APACHE II评分。
The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785–0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores. Four novel protein biomarkers encoded by the miRNA target genes were identified for patients with sepsis. The combined analysis of the four proteins indicated that their predictive value for sepsis prognosis was better than the values for the SOFA score and APACHE II score.