Circulating expression of Hsa_circRNA_102893 contributes to early gestational diabetes mellitus detection

Abstract

Due to a poor availability of reliable biomarkers, detecting gestational diabetes mellitus (GDM) in early pregnancy remains a challenge. Novel biomarkers like Circular RNAs (circRNAs) may be a promising diagnostic tool. The aim of this study was (a) to identify circRNAs deregulated in GDM and (b) evaluate the potential of circRNAs in detecting GDM. The circRNAs expression profiling in 6 paired women (with and without GDM) was measured by microarray. The levels of five most relevant circRNAs were validated in 12 paired participants by qRT-PCR. To verify the reproducibility of qRT-PCR, significantly differential expressed circRNA levels were confirmed in 18 paired participants. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The areas under ROC curves of hsa_circRNA_102893 were 0.806 (95% CI 0.594-0.937) and 0.741 (0.568-0.872) in training set and test set, respectively. Circulating circRNAs reflect the presence of GDM. Hsa_circRNA_102893 may be a potential novel and stable noninvasive biomarker for detecting GDM in early pregnancy.

Figure 1

The expression profiles of circRNAs compared between GDM and paired adjacent control group. The Scatter-Plot (A) is a visualization method used for assessing the circRNAs expression variation (or reproducibility) between pregnant women with GDM and control group. The X and Y axis values in the scatter-Plot are the normalized signal values of the average normalized signal values (log2 scaling) of each group of samples. The green lines are Fold Change Lines. The circRNAs above the top green line and below the bottom green line indicate that the change of circRNAs in the two compared samples exceeds 2.0 fold. Volcano Plots (B): the vertical lines correspond to 2.0-fold up and down, respectively, and the horizontal line represents a p-value of 0.05 (t-test). The red point in the plot represents the differentially expressed circRNAs with statistical significance. Histogram (C): among 3678 circRNAs, a total of 2678 circRNAs were detected with 2.0-fold change and p ≤ 0.05 (t-test), of which 1532 were up-regulated and 1146 were down-regulated.

Figure 2

Circulating hsa_circRNA_102893 expressed in the plasma of pregnant women with GDM in comparison with healthy pregnant women (control). (A) Relative expression levels of hsa_circRNA_102893 with their corresponding P values (Paired t-test) in the training set and test set. Scatter plots show relative expression levels. The orange boxes and the horizontal bars represent the mean and the standard error, respectively. (B) ROC curves of hsa_circRNA_102893 and the AUC, sensitivity, specificity and cutoff point in the training set and test set. Red point is corresponding to Youden index.