Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood
Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood
复制标题
发现并验证 hsa_circ_0001953 作为人类血液中增殖性糖尿病视网膜病变的潜在生物标志物
DOI：
10.1111/aos.14585
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发表时间：
2020-09-10
影响因子：
3.4
通讯作者：
Wang, Jiawei
中科院分区：
文献类型：
--
作者：
Wu, Zheming;Liu, Bing;Wang, Jiawei
目的探讨全血中的环状RNA(CircRNAs)能否作为增殖性糖尿病视网膜病变(PDR)的新的非侵入性生物标志物。方法对34例健康受试者、34例PDR患者和34例非增殖型糖尿病视网膜病变(NPDR)患者进行回顾性横断面研究。采用高通量全转录组测序的方法研究CircRNAs在全血中的表达谱，并通过实时定量聚合酶链式反应(qRT-PCR)对候选的CircRNAs进行验证。受试者工作特征(ROC)分析评估了这些候选CircRNA区分PDR患者、NPDR患者和健康受试者的能力。最后，构建了基于候选CircRNAs的CircRNA-miRNA-mRNA网络。结果采用测序和定量RT-PCR法，发现hsa_CIRC_0001953在糖尿病视网膜病变患者中明显高于其他两组。统计学分析显示，hSA_CIRC_0001953在糖尿病视网膜病变患者中的表达水平与糖尿病病程和糖化血红蛋白水平呈正相关。受试者工作特征(ROC)曲线分析显示，hSA_CIRC_0001953具有较高的鉴别诊断准确率，曲线下面积(AUC)分别为0.87和0.92。HSA_CIRC_0001953的CircRNA-miRNA靶向基因网络表明，hSA_CIRC_0001953可与数十个miRNA相互作用，其中一些靶向mRNA可能参与了糖尿病的发病机制。结论全血中hSA_CIRC_0001953可能是一种新的诊断PDR的生物标志物和潜在的治疗靶点。
Purpose This study aimed to determine whether circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for proliferative diabetic retinopathy (PDR). Methods This retrospective cross-sectional study comprised 34 healthy participants, 34 PDR patients and 34 non-proliferative DR (NPDR) patients. High-throughput whole transcriptome sequencing was performed to explore the expression profile of circRNAs in the whole blood, and the candidate circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis evaluated the ability of these candidate circRNAs in discriminating PDR patients from NPDR patients and healthy subjects. Finally, the networks of circRNA-miRNA-mRNA based on the candidate circRNAs were constructed. Results Using sequencing and qRT-PCR, hsa_circ_0001953 was found to be elevated in PDR patients in contrast with the other two groups. Statistical analysis showed that the expression levels of hsa_circ_0001953 in PDR patients were positively related to the duration of diabetes and HbAc1. Receiver operating characteristic (ROC) curve analysis revealed that hsa_circ_0001953 was associated with a high diagnostic accuracy in discriminating PDR patients from NPDR patients and healthy controls, resulting in an area under the curve (AUC) of 0.87 and 0.92, respectively. The circRNA-miRNA-target gene networks for hsa_circ_0001953 showed that hsa_circ_0001953 could interact with dozens of miRNAs and some targeted mRNAs have been potentially involved in the pathogenesis of diabetes. Conclusion The present findings indicate that hsa_circ_0001953 in the whole blood may serve as a novel diagnostic biomarker and potential therapeutic target for PDR.