4种转录组标志物用于活动性结核的诊断研究

Use of four biomarkers derived from transcriptional signatures for the diagnosis of active tuberculosis

目的探究转录组学结果对筛选用于诊断活动性结核的宿主蛋白靶标的指导意义。方法检测并分析30例活动性结核和30例非结核全血中FCGR1A、DUSP3、SEPT4和BATF2蛋白的差异。对于差异蛋白,使用160份活动性结核和116份非结核进行验证。结果在30例活动性结核和30例非结核患者队列中,活动性结核患者全血FCGR1A蛋白水平为2.424 ng/mL,高于非结核患者组2.154 ng/mL(Z=-2.979,P=0.036),其他几个靶标的全血蛋白水平在两组中差异无统计学意义。在验证队列中,全血FCGR1A蛋白水平在活动性结核患者组(3.377 ng/mL)依旧显著高于非结核患者组2.003 ng/mL(Z=-5.738,P<0.001),ROC曲线分析表明其对活动性结核和非结核肺病具有一定的区分能力AUC=0.702(P<0.01)。结论宿主转录标志物和其对应蛋白对活动性结核诊断价值存在差异,提示转录组学结果对指导研制宿主免疫检测试剂指导价值有限。

This study explored the implications of transcriptomic results for screening host protein targets in the diagnosis of active tuberculosis.The levels of FCGR1A,DUSP3,SEPT4 and BATF2 proteins in the whole blood of 30 patients with active tuberculosis and 30 patients with other non-tuberculosis disease were measured,and the differences were analyzed.A total of 160 active tuberculosis samples and 116 non-tuberculosis samples were used to verify this difference.The whole blood FCGR1A protein level was significantly higher in the 30 patients with active tuberculosis(2.424 ng/mL)than the 30 patients with non-tuberculosis disease 2.154 ng/mL(Z=-2.979,P=0.036).No significant difference was observed in other protein levels in the whole blood between groups.In the verification cohort,the level of whole blood FCGR1A protein was significantly higher in the active tuberculosis group(3.377 ng/mL)than the non-tuberculosis group 2.003 ng/mL(Z=-5.738,P<0.001).In addition,ROC curve analysis indicated that the FCGR1A protein level distinguished active tuberculosis from non-tuberculosis lung disease(AUC=0.702,P<0.01).In general,differences exist between host transcriptional markers and their translated proteins in the diagnosis of active tuberculosis,thus suggesting that the transcriptomic results have limited value in guiding the development of host immune detection reagents.