Metabolomic identification of novel diagnostic biomarkers in ectopic pregnancy
Ectopic pregnancy (EP) is a potentially life-threatening condition and early diagnosis still remains a challenge, causing a delay in management leading to tubal rupture.
To identify putative plasma biomarkers for the detection of tubal EP and elucidate altered biochemical pathways in EP compared to intrauterine pregnancies.
This case–control study included prospective recruitment of 39 tubal EP cases and 89 early intrauterine pregnancy controls. Plasma samples were biochemically profiled using proton nuclear magnetic resonance spectroscopy (1H NMR). To avoid over-fitting, datasets were randomly divided into a discovery group (26 cases vs 60 controls) and a test group (13 cases and 29 controls). Logistic regression models were developed in the discovery group and validated in the independent test group. Area under the receiver operating characteristics curve (AUC), 95% confidence interval (CI), sensitivity, and specificity values were calculated.
In total 13 of 43 (30.3%) metabolite concentrations were significantly altered in EP plasma (p < 0.05). Metabolomic profiling yielded significant separation between EP and controls (p < 0.05). Independent validation of a two-metabolite model consisting of lactate and acetate, achieved an AUC (95% CI) = 0.935 (0.843–1.000) with a sensitivity of 92.3% and specificity of 96.6%. The second metabolite model (d-glucose, pyruvate, acetoacetate) performed well with an AUC (95% CI) = 0.822 (0.657–0.988) and a sensitivity of 84.6% and specificity of 86.2%.
We report novel metabolomic biomarkers with a high accuracy for the detection of EP. Accurate biomarkers could potentially result in improved early diagnosis of tubal EP cases.
KeywordsEctopic pregnancy Metabolomics Nuclear magnetic resonance spectroscopy Biomarker Metabolite
OT supervised the experiment, manuscript writing and performed statistical data analysis; OT, AC, CK performed specimen collection; SFG supervised all experimental procedures; PK, AY performed the experiments and analyzed the raw data; RBS, SE, DU, IM supervised and designed the experiment and manuscript writing and all authors reviewed the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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