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循环成纤维细胞生长因子 21 作为人类稽留流产的潜在生物标志物。

Circulating fibroblast growth factor 21 as a potential biomarker for missed abortion in humans.

机构信息

The Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, People's Republic of China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, People's Republic of China.

State Key Laboratory of Pharmaceutical Biotechnology, the University of Hong Kong, Hong Kong SAR, People's Republic of China; Department of Medicine, the University of Hong Kong, Hong Kong SAR, People's Republic of China.

出版信息

Fertil Steril. 2021 Oct;116(4):1040-1049. doi: 10.1016/j.fertnstert.2021.05.098. Epub 2021 Jun 21.

Abstract

OBJECTIVE

To investigate whether serum levels of fibroblast growth factor 21 (FGF21) and fatty acid-binding protein-4 (FABP4) are associated with missed abortion (MA) in humans.

DESIGN

Cross-sectional study.

SETTING

University-affiliated hospital.

PATIENT(S): Patients with MA at 8-12 weeks of gestation.

INTERVENTION(S): None.

MAIN OUTCOME MEASURES(S): Serum levels of FGF21 and FABP4 were tested by enzyme-linked immunosorbent assay. Placental samples were collected during dilation and curettage surgery, and the expression of FGF21 and its related genes were measured using quantitative polymerase chain reaction.

RESULT(S): In the discovery cohort, 78 patients with MA and 79 healthy pregnant women matched for maternal age and body mass index were nested from a prospective cohort. Circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to the levels in the healthy controls. A single measurement of FGF21 serum level effectively discriminated MA with an area under the receiver operating characteristics curve of 0.80 (95% confidence interval: 0.73-0.87). Importantly, in our external validation cohort that comprised subjects with MA (n = 34) or induced abortion (n = 27), the FGF21 serum levels achieved an area under the receiver operating characteristics curve of 0.85 (95% confidence interval: 0.75-0.96) when identifying those with MA. Nevertheless, expression of FGF21 in the placenta was not associated with its serum concentration. Placental tissues from patients with MA exhibited impaired FGF21 signaling.

CONCLUSION(S): Our results suggested that serum levels of FGF21 and FABP4 were associated with MA. Circulating FGF21 may serve as a potential biomarker for the recognition of MA.

摘要

目的

探讨成纤维细胞生长因子 21(FGF21)和脂肪酸结合蛋白 4(FABP4)的血清水平是否与人类稽留流产(MA)相关。

设计

横断面研究。

地点

大学附属医院。

患者

妊娠 8-12 周的 MA 患者。

干预

无。

主要观察指标

通过酶联免疫吸附试验检测 FGF21 和 FABP4 的血清水平。在扩张刮宫术期间采集胎盘样本,并通过定量聚合酶链反应测量 FGF21 及其相关基因的表达。

结果

在发现队列中,从前瞻性队列中嵌套了 78 例 MA 患者和 79 例年龄和体重指数匹配的健康孕妇。与健康对照组相比,MA 患者的循环 FGF21 和 FABP4 水平显著升高。单次 FGF21 血清水平测量可有效区分 MA,受试者工作特征曲线下面积为 0.80(95%置信区间:0.73-0.87)。重要的是,在我们的外部验证队列中,包括 MA(n=34)或人工流产(n=27)的患者,当识别 MA 患者时,FGF21 血清水平的受试者工作特征曲线下面积达到 0.85(95%置信区间:0.75-0.96)。然而,胎盘 FGF21 的表达与血清浓度无关。MA 患者的胎盘组织表现出 FGF21 信号受损。

结论

我们的结果表明,FGF21 和 FABP4 的血清水平与 MA 相关。循环 FGF21 可能是识别 MA 的潜在生物标志物。

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