aGVHD患者循环MicroRNA变化规律和机制研究及预警与辅助诊断价值评估

项目名称： aGVHD患者循环MicroRNA变化规律和机制研究及预警与辅助诊断价值评估

项目编号： No.81501821

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张春燕

作者单位： 中国人民解放军总医院

项目金额： 18万元

中文摘要： 急性移植物抗宿主病是异基因造血干细胞移植后严重并发症之一，发生率高达35％至64％。目前临床上缺乏血清学指标来无创性地早期诊断aGVHD和监测治疗反应，导致aGVHD发现时已进展严重，影响移植生存率和生存质量。前期研究中，我们使用ABI microRNA寡密度芯片在血清中初步筛选出6个miRNA与aGVHD发生发展密切相关，存在aGVHD早期预警和辅助诊断的潜能。因此，我们拟通过收集病例，验证前期结果，监测aGVHD发生前到发生时血清中miRNAs动态变化，使用软件预测miRNA下游分子机制并在细胞水平作初步探索，阐明miRNAs参与aGVHD发生发展的作用机制，建立miRNA联合预警和诊断aGVHD的模型，进一步通过临床前瞻性试验评价miRNA用于aGVHD预警的临床应用价值，找到有效的、临床可用的、无创的aGVHD预警指标和监测指标，为临床GVHD预警和辅助诊断提供新的无创的诊断途径。

中文关键词： 循环miRNA；移植物抗宿主病；预警；辅助诊断；信号通路

英文摘要： Acute graft versus host disease (aGVHD) is one of the severe complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with an incidence of 35 to 64%. Currently, they have not yet found a suitable noninvasive blood index or model to help early warning and diagnosis of aGVHD. Once the clinical performance is significant, the immune response has been so strong that it is dangerous and hard to be controlled, which would reduce transplant survival rate and quality of life. In our previous study, we profiled miRNAs in serum pools from patients with aGVHD (grades II-IV) and non-aGVHD controls by ABI microRNA array and preliminary find 6 miRNAs are related to the development and occurrence of aGVHD. Therefore, we intend to validate the results by monitoring the dynamic change of serum miRNAs during allo-HSCT, predicting downstreams of miRNAs by softwares and exploring the molecular mechanisms at the cellular level. And then we will collect cases and establish model for early warning and diagnosis of aGVHD by combining with clinical information and miRNAs. Finally, we intend to find the effective and clinical available, non-invasive warning indicators and auxiliary diagnosis indicators for aGVHD.

英文关键词： microRNA;Acute Graft-versus-host disease;prediction;diagnosis;signaling pathway