血清外泌体miR-451a在弥漫大B细胞淋巴瘤治疗监测中的意义

目的 探索血清外泌体miR-451a在弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma, DLBCL）中的水平及其在治疗监测中的价值。方法 本研究共纳入56例DLBCL患者，56例健康对照者。收集新发DLBCL患者治疗前、化疗2~4疗程及化疗结束后血清样本，并同时收集健康人血液标本， 提取血清中的外泌体RNA，并进行实时荧光定量PCR（quantitative real time polymerase chain reaction, qRT-PCR），用受试者工作特征（receive operator characteristic, ROC）曲线判定miR-451a的诊断效能，用各时点收集的血清样本动态分析血清外泌体miR-451a水平与化疗效果之间的关系。结果 56例DLBCL患者与56例健康对照者相比，DLBCL患者血清外泌体miR-451a水平下降（P<0.000 1），在两组受试者间用miR-451a诊断DLBCL的曲线下面积(AUC)为0.737（95%CI0.645~0.816）。在随访到的43例DLBCL患者中，化疗后获得完全缓解或者部分缓解的患者其血清外泌体miR-451a水平较化疗前有所上升（P<0.05），与配对的健康人水平差异无统计学意义（P>0.05）；化疗后未获得缓解的患者，其血清外泌体miR-451a水平较化疗前无明显变化（P>0.05），且仍然低于配对的健康人水平（P<0.05）；化疗完成后在未缓解者与缓解者之间进行鉴别，血清miR-451a的AUC为0.867（95%CI0.728~0.951）。结论 血清外泌体miR-451a水平动态监测有助于DLBCL化疗过程中的疗效（是否缓解）判断。

The Value of Circulating Exsomal miR-451a to Monitor Therapy Response in Diffuse Large B Cell Lymphoma

Objective To investigate the expression level of circulating exsomal miR-451a and its significances in therapy monitoring in diffuse large B cell patients. Methods We isolated exsomal RNAs fractions from serum of 56 DLBCL patients before treatment， during treatment and after treatment. The serum of 56 healthy controls was collected at the same time. Quantitative real time polymerase chain reaction （qRT-PCR） were performed to detected the expression level of circulating exsomal miR-451a. Receive operater characteristic (ROC) curve was performed to comfirm the diagnostic efficiency of miR-451a. Chemotherapy effect corresponding with miR-451a was analyzed. Results Circulating exsomal miR-451a was down-expression in DLBCL compared with healthy controls (P<0.000 1)，and the area under the ROC curve (AUC) was 0.737 （95%CI0.645-0.816）. In 43 patients who had complete follow-up information, the patients who obtained remission, including complete remission （CR） and partial remission （PR）, had the levels of circulating exsomal miR-451a gradually increased. While in patients who did not get remission，including stable disease （SD） and progression disease （PD）, had no significant changes of circulating exsomal miR-451a. Conclusion Circulating exsomal miR-451a may be an potential indicator for therapy response monitoring in DLBCL.