Title | Circulating microRNA miR-323-3p as a biomarker of ectopic pregnancy. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Zhao Z, Zhao Q, Warrick J, Lockwood CM, Woodworth A, Moley KH, Gronowski AM |
Journal | Clin Chem |
Volume | 58 |
Issue | 5 |
Pagination | 896-905 |
Date Published | 2012 May |
ISSN | 1530-8561 |
Keywords | Adolescent, Biomarkers, Case-Control Studies, Chorionic Gonadotropin, Female, Humans, MicroRNAs, Pregnancy, Pregnancy, Ectopic, Progesterone, Real-Time Polymerase Chain Reaction, Retrospective Studies, Sensitivity and Specificity |
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. |
DOI | 10.1373/clinchem.2011.179283 |
Alternate Journal | Clin Chem |
PubMed ID | 22395025 |
Grant List | T32 DK 007296 / DK / NIDDK NIH HHS / United States |
Related Faculty:
Zhen Zhao, Ph.D.