title: 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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Pregnancy-associated miRNAs, especially miR-323-3p, added substantial diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Zhao
authors.forename: Joshua
authors.initials: J
authors.lastname: Warrick
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lockwood
authors.forename: Alison
authors.initials: A
authors.lastname: Woodworth
authors.forename: Kelle H
authors.initials: KH
authors.lastname: Moley
authors.forename: Ann M
authors.initials: AM
authors.lastname: Gronowski
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000175:diagnosis*; D011374:Progesterone / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; C573188:MIRN323 microRNA, human; D035683:MicroRNAs; D011374:Progesterone