Abstract:   Objective To screen and determine whether serum hsa_circ_0000615 can be used as a new non invasive biomarker for proliferative diabetic retinopathy (PDR). Design Prospective case series. Participants  A simple random sampling method was used to select 50 non-diabetic volunteers (as control group), 48 patients with type-2 diabetes mellitus (T2DM), 50 PDR patients and 50 patients with non-PDR (NPDR). Methods  High throughput whole transcriptome sequencing was performed to explore the expression profile of serum circRNAs, and the candidate circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis evaluated the ability of serum hsa_circ_0000615 in discriminating PDR patients from NPDR patients, T2DM patients and control subjects. Main Outcome Measures  Serum circRNAs expression profile and has_cic_0000615 expression level. Results  By sequencing and qRT-PCR, serum hsa_circ_0000615 expression in PDR patients [12.015 (8.530, 14.325)] was significantly higher than that in control group [3.998 (3.220, 5.156)], T2DM group [5.118 (3.895, 7.247)] and NPDR group [5.250 (4.045, 7.763)] (all P＜0.05).  By correlation analysis and linear regression analysis, the level of hsa_circ_0000615 expression was positively correlated with the course of diabetes (r=0.429, P＜0.001) and the level of glycated hemoglobin (r=0.567, P＜0.001). ROC curve analysis showed that the area under curve of serum hsa_circ_0000615 was 0.803±0.036 (95% CI: 0.731～0.874), 0.796±0.039 (95% CI: 0.719～0.872) and 0.976±0.010 (95%CI: 0.956～0.997), respectively. Conclusion  The present findings indicate that serum hsa_circ_ 0000615 may serve as a novel diagnostic biomarker and potential therapeutic target for PDR.

Key words:  CircRNAs, Proliferative diabetic retinopathy, Biomarkers