PRDM1和GATA2基因mRNA作为活动性结核和潜伏感染鉴别诊断标志物的可能性研究

The m RNA of PRDM1 and GATA2 as biomarkers to distinguish patients with active tuberculosis from latent infection

目的活动性结核病的诊断仍然是结核病防治的重点和难点,差异表达基因有望成为结核病新的诊断靶标。本研究通过检测结核分枝杆菌不同感染状态下人外周血中PR/SET域1(PR/SET domain 1,PRDM1)和GATA结合蛋白2(GATA binding protein 2,GATA2)基因的mRNA表达,分析其作为诊断标志物的能力。方法收集活动性结核病患者、结核分枝杆菌潜伏感染者和健康人外周血,荧光定量PCR检测外周血单个核细胞中PRDM1和GATA2的m RNA水平,分析各组受试者PRDM1和GATA2基因表达差异及其鉴别活动性结核和潜伏感染的诊断能力。结果活动性结核病患者外周血单个核细胞中PRDM1和GATA2的表达显著低于潜伏感染者和健康人(H=69.27,P<0.0001;H=37.97,P<0.0001)。PRDM1鉴别诊断活动性结核和潜伏感染的曲线下面积为0.8967,灵敏度为80.22%,特异度为87.1%。GATA2鉴别诊断活动性结核和潜伏感染的曲线下面积为0.8061,灵敏度为82.35%,特异度为70.97%。PRDM1和GATA2联合诊断活动性结核和潜伏感染的曲线下面积为0.935,诊断的灵敏度为76.9%,特异度为100%。结论外周血单个核细胞中PRDM1和GATA2的mRNA表达水平是鉴别活动性结核和潜伏感染者的潜在标志物,有助于活动性结核的辅助诊断。

Objective The diagnosis of tuberculosis is still the focus and difficulty of tuberculosis control.The differentially expressed genes of human beings are expected to become new diagnostic targets for tuberculosis.This study detected the mRNA expression of PR/SET domain 1(PRDM1)and GATA binding protein 2(GATA2)in human peripheral blood under different infection states of Mycobacterium tuberculosis,and analyzed their ability as diagnostic biomarkers.Methods The peripheral blood from patients with active tuberculosis,individual with latent tuberculosis infection and healthy controls was collected.The m RNA levels of PRDM1 and GATA2 in peripheral blood were detected by fluorescence quantitative PCR.The different expression and diagnostic value of PRDM1 and GATA2 were analyzed by the statistic software.Results The expression of PRDM1 and GATA2in patients with active tuberculosis was significantly lower than those of latent tuberculosis infection and healthy controls(H=69.27,P<0.0001;H=37.97,P<0.0001).The area under curve of PRDM1 in differential diagnosis of active tuberculosis and latent tuberculosis infection was 0.8967,with sensitivity of 80.22%and specificity of 87.1%,the area under curve of GATA2 was 0.8061,the sensitivity and specificity was 82.35%and 70.97%respectively.When these two genes together was used to distinguish active tuberculosis from latent tuberculosis infection,the area under curve was 0.935,the sensitivity and specificity was 76.9%and 100%respectively.Conclusion The mRNA expression of PRDM1 and GATA2 in peripheral blood were potential biomarkers for diagnosis of tuberculosis,and may assist diagnosis of active tuberculosis.