Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood
Zheming Wu, Bing Liu, Yan Ma, Haisong Chen, Jing Wu, Jiawei Wang
Abstract
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.