Department of Obstetrics and Gynecology, Beaumont Health System, Royal Oak, MI, USA.
Oakland University-William Beaumont School of Medicine, Rochester, MI, USA.
Metabolomics. 2019 Oct 19;15(11):143. doi: 10.1007/s11306-019-1607-1.
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 (H 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.
宫外孕（EP）是一种潜在危及生命的疾病，早期诊断仍然具有挑战性，这导致处理延迟，从而导致输卵管破裂。
确定用于检测输卵管异位妊娠的潜在血浆生物标志物，并阐明与宫内妊娠相比异位妊娠中改变的生化途径。
这项病例对照研究包括前瞻性招募 39 例输卵管异位妊娠病例和 89 例早期宫内妊娠对照。使用质子核磁共振波谱（H NMR）对血浆样本进行生化分析。为避免过度拟合，数据集随机分为发现组（26 例对 60 例对照）和测试组（13 例对 29 例对照）。在发现组中建立逻辑回归模型，并在独立的测试组中进行验证。计算曲线下的面积（AUC）、95%置信区间（CI）、敏感性和特异性值。
共有 13 种（30.3%）代谢物浓度在 EP 血浆中显著改变（p < 0.05）。代谢组学分析可显著区分 EP 和对照组（p < 0.05）。由乳酸盐和醋酸盐组成的两种代谢物模型的独立验证，AUC（95%CI）为 0.935（0.843-1.000），灵敏度为 92.3%，特异性为 96.6%。第二个代谢物模型（D-葡萄糖、丙酮酸、乙酰乙酸盐）表现良好，AUC（95%CI）为 0.822（0.657-0.988），灵敏度为 84.6%，特异性为 86.2%。
我们报告了用于检测 EP 的具有高准确性的新型代谢组学生物标志物。准确的生物标志物可能会导致对输卵管异位妊娠病例的早期诊断得到改善。
