血清miR-17-92基因簇对视网膜母细胞瘤诊断价值的研究

Value of serum miR-17-92 cluster in diagnosis of retinoblastoma

摘要:

目的 分析血清miR-17-92基因簇对视网膜母细胞瘤（RB）的诊断价值。方法 采用实时定量PCR法检测20例RB患儿、20名健康对照者的血清miR-17-92基因簇表达水平，分析其在不同分期RB患儿的表达差异及综合治疗前后的变化，并采用ROC曲线判断其对RB的诊断价值。结果 RB患儿血清中miR-17-92基因簇成员miR-17-3P、miR-17-5P、miR-18a和miR-20a的相对表达量均高于健康对照组，以miR-18a升高更为显著，差异均有统计学意义（P < 0.05）；两组miR-19a、miR-19b-1和miR-92a-1相对表达量的差异无统计学意义（P > 0.05）。miR-17-5P、miR-17-3P、miR-18a和miR-20a表达量在早中期和晚期RB患儿之间的差异均无统计学意义（P > 0.05），但综合治疗后表达量显著降低（P < 0.05）。miR-17-3P、miR-17-5P、miR-18a和miR-20a对RB诊断价值的曲线下面积（AUC）分别为0.770、0.755、0.828和0.665，以miR-18a的AUC最大，并具有较好的灵敏度（90%）和特异度（65%）。结论 miR-17-92基因簇的miR-17-3P、miR-17-5P、miR-18a和miR-20a在RB患儿血清中高表达，miR-18a有可能作为RB诊断的新指标。

Abstract:

Objective To investigate the value of serum miR-17-92 cluster in the diagnosis of retinoblastoma (RB). Methods Serum samples were collected from 20 children with RB and 20 healthy controls. Quantitative real-time PCR was used to measure the expression of miR-17-92 cluster. The expression of miR-17-92 cluster was compared between children with different stages of RB and the changes in the expression of miR-17-92 cluster after multimodality therapy were analyzed. The receiver operating characteristic (ROC) curve was used to investigate the value of serum miR-17-92 cluster in the diagnosis of RB. Results Compared with the healthy controls, the children with RB had signifcantly higher relative expression of miR-17-3P, miR-17-5P, miR-18a, and miR-20a in serum (P < 0.05), and miR-18a showed the greatest increase. There were no signifcant differences in the relative expression of miR-19a, miR-19b-1, and miR-92a-1 between children with RB and healthy controls (P > 0.05). There were no signifcant differences in the expression of miR-17-5P, miR-17-3P, miR-18a, and miR-20a between the children with early-to-moderate stage of RB and those with advanced stage of RB (P >  0.05), but there were signifcant reductions after multimodality therapy (P < 0.05). In the diagnosis of RB, the areas under the ROC curve (AUCs) for serum miR-17-3P, miR-17-5P, miR-18a, and miR-20a were 0.770, 0.755, 0.828, and 0.665 respectively, and miR-18a had the largest AUC, with a sensitivity of 90% and a specifcity of 65%. Conclusions miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed in the serum of children with RB, and miR-18a may be used as a new marker for the diagnosis of RB.