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

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 58; no. 5; pp. 896 - 905
• Main Authors: ZHEN ZHAO, QIUHONG ZHAO, WARRICK, Joshua, LOCKWOOD, Christina M, WOODWORTH, Alison, MOLEY, Kelle H, GRONOWSKI, Ann M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for Clinical Chemistry 01-05-2012; Oxford University Press
• Subjects: Abdomen; Adolescent; Analytical, structural and metabolic biochemistry; Autoimmune diseases; Biological and medical sciences; Biomarkers; Biomarkers - blood; Case-Control Studies; Chorionic Gonadotropin - blood; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunoassays; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; MicroRNAs - blood; Molecular biophysics; Pain; Pregnancy; Pregnancy, Ectopic - diagnosis; Progesterone - blood; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; Shipments; Statistical analysis; Gene silencing; RNA interference; Pregnancy disorders; Clinical biology; Micro RNA; Biological marker; Biological indicator; Biochemistry; Chromosome A3; Molecular biology; Ectopic pregnancy
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2011.179283

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.
This study was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping and received a diagnosis of viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were measured by immunoassays. The serum concentrations of miRNAs miR-323-3p, miR-517a, miR-519d, and miR-525-3p were measured with TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers, both as single markers and as multimarker panels for EP.
Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA cases than in VIP cases (P < 0.01). In contrast, the concentration of miR-323-3p was significantly increased in EP cases, compared with SA and VIP cases (P < 0.01). As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed specificity of 90%). In comparison, the combined panel of hCG, progesterone, and miR-323-3p yielded the highest sensitivity (77.8%, at a fixed specificity of 90%). A stepwise analysis that used hCG first, added progesterone, and then added miR-323-3p yielded a 96.3% sensitivity and a 72.6% specificity.
Pregnancy-associated miRNAs, especially miR-323-3p, added substantial diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP.