Circulating MicroRNA miR-323-3p as a Biomarker of Ectopic Pregnancy

Abstract

BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping, and were diagnosed with viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were determined by immunoassays. Serum miR-323-3p, miR-517a, miR-519d, and miR-525-3p concentrations were measured using TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA than in VIP. In contrast, the concentration of miR-323-3p was significantly elevated in EP as compared to SA and VIP. As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed-specificity of 90%). Comparatively, combined hCG, progesterone, and miR-323-3p panel yielded the highest sensitivity of 77.8% (at a fixed-specificity of 90%). A stepwise analysis using hCG, then progesterone, and then miR-323-3p resulted in 96.3% sensitivity and 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added significant diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP.

MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy

“…In the present study, we measured the concentration of 21 pregnancy-associated miRNAs as well as hCG and progesterone in serum samples from patients with EP, VIP, and SA. Of five miRNAs differentially expressed between these patients, miR-873 and miR-223 were significantly downregulated in EP compared with SA and did not change significantly according to GA. MiR-323 was also significantly higher in EP than in VIP and SA, similar to a previously study[8], and the combined assessment of miR-323-3p, hCG, and progesterone showed a sensitivity of 67.65 % for the detection of EP at a fixed specificity of 90%, and in combination with other markers showed that the combination of miR-323 with hCG and progesterone and miR-873 had the highest AUC for the prediction of EP. As a single marker, miR-873 had the highest sensitivity at 61.76 % (at a fixed specificity of 90%), suggesting its potential as a biomarker for the early detection of EP.…”

“…To detect miRNAs with diagnostic potential for pregnancy-associated complications, researchers have compared the serum concentrations of miRNAs between patients with specific disorders and healthy controls, which resulted in the identification of a large number of differentially expressed miRNAs, many of which were confirmed as promising biomarkers for specific disorders. Zhao et al examined the diagnostic accuracy of miRNAs for the detection of EP and showed that miR-517a, miR-519d, and miR-525-3p were significantly lower, whereas miR-323-3p was significantly higher in EP and SA than in VIP[8]. Furthermore, the combined assessment of miR-323-3p, hCG, and progesterone showed a sensitivity of 77.8 % for the detection of EP at a fixed specificity of 90%.…”

“…For hCG, serial monitoring every 48 h is necessary for a positive diagnosis of EP; an increase in hCG of ≥66% in 48 h is associated with VIP, whereas an increase of <50% is associated with abnormal pregnancy including EP [6, 7]. However, these measurements cannot identify the location of the gestational sac and are associated with high false-positive and false-negative rates, in addition to putting the patient at risk of tubal rupture in between measurements [8]. Furthermore, these markers are not effective for distinguishing between EP and spontaneous abortion [9].…”

Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease

“…[12][13][14][15][16][17][18][19][20] Here, we show that plasma miRNAs can be used as biomarkers for aGVHD. We found that the plasma levels of 6 miRNAs (miR-423, miR-199a-3p, miR-93*, miR-377, miR-155, and miR-30a) were significantly elevated in the plasma of aGVHD patients when compared with non-GVHD patients.…”

“…[9][10][11] Circulating miRNAs have the potential to serve as novel, noninvasive biomarkers for various diseases such as cancer, cardiovascular disease, sepsis, organ transplant rejection, liver injury, ectopic pregnancy, diabetes, and infection. [12][13][14][15][16][17][18][19][20] In this study, we have identified a group of plasma miRNAs as potential biomarkers for aGVHD. We found that 6 miRNAs (miR-423, miR-199a-3p, miR-93*, miR-377, miR-155, and miR30a) were significantly upregulated in the plasma of aGVHD patients when compared with non-GVHD patients after HCT.…”