Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM

Lina Wang,Xiubin Sun,Siyuan Li,Mengru Xu,Chunyan Yang,Guanghui Cheng,Junfeng Zhang,Bao Jiang

doi:10.1186/s12967-021-03195-5

Abstract

BackgroundGestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM.MethodsWe performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages.ResultsPlasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001).ConclusionPlasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

Highlights

Gestational Diabetes Mellitus (GDM) is a metabolic disorder, in which hyperglycemia is developed during pregnancy in women without diabetes
There were no obvious differences with regard to the age, height, delivery gestational age, gestation (G), production (P) of women and neonatal weight in Gestational diabetes mellitus (GDM) and normal glucose tolerant (NGT)
Even if the isolates are rich in exosomes, it cannot clearly indicate that circRNAs are derived from exosomes

Summary

Introduction

Gestational Diabetes Mellitus (GDM) is a metabolic disorder, in which hyperglycemia is developed during pregnancy in women without diabetes. It is reported that GDM diagnosed at 24–28 weeks of gestation have already affected fetal development [4]. GDM affects maternal and fetal health substantially and it is of necessity to screen the predictive and diagnostic biomarkers for GDM in the early stage of pregnancy [5]. Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. It is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. We attempted to identify the exosomal circRNA biomarkers for detecting early GDM

Methods

Results

Conclusion