整合iTRAQ-2DLC-MS/MS和Solexa测序技术的一组新的诊断耐多药肺结核病的血清标志物

来源 :2015中国转化医学大会暨中国转化医学联盟成立大会 | 被引量 : 0次 | 上传用户:jinmin511
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  耐药肺结核病特别是耐多药肺结核病(MDR-TB)的流行对当今肺结核病的有效治疗提出了重大挑战.本研究通过iTRAQ-2DLC-MS/MS和Solexa测序技术筛选了MDR-TB、非耐药肺结核病(DS-TB)和正常对照间蛋白组学和转录组学的差异,发现在MDR-TB组有50个蛋白质以及43个差异miRNAs与DS-TB组和正常对照组组均存在差异.进一步靶基因预测和整合分析,发现22.00%的差异蛋白质和32.56%的差异miRNAs间能够建立渊控关系网络,且多存在于补体和凝血途径,从中我们选取了有对应凋控关系的3对蛋白质-miRNAs: CD44antigen(CD44)-miR-4433b-5p,Coagulation factor Ⅺ (F11)-miR-424-5p,和kininogen-1(KNG1)-miR-199b-5p进行验证.验证实验发现KNGl和miR-424-5p在MDR-TB、DS-TB和正常对照3组间均存在显著差异,并且KNGl与miR-199b-5p存在负相关(r=-0.232, P=0.017).F11和miR-4433b-5p只在MDR-TB和DS-TB间有差异,CD44和miR-199b-5p只在MDR-TB和正常对照间有差异.我们最终确立了以CD44,KNGl,miR-4433b-5p,miR-424-5p,miR-199b-5p为节点的MDR-TB诊断模型.我们的研究为MDR-TB提供了一组新的诊断标志物,为阐明机体蛋白组学和转录组学标志物在MDR-TB发病中的作用提供了新的实验依据.
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