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基于六种血浆生物标志物联合分析的子宫内膜异位症无创诊断。

Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers.

机构信息

Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven University Fertility Centre, Herestraat 49, B-3000 Leuven, Belgium.

出版信息

Hum Reprod. 2010 Mar;25(3):654-64. doi: 10.1093/humrep/dep425. Epub 2009 Dec 9.

DOI:10.1093/humrep/dep425
PMID:20007161
Abstract

BACKGROUND

Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. The aim of this study was to evaluate the combined performance of six potential plasma biomarkers in the diagnosis of endometriosis.

METHODS

This case-control study was conducted in 294 infertile women, consisting of 93 women with a normal pelvis and 201 women with endometriosis. We measured plasma concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive protein (hsCRP), and cancer antigens CA-125 and CA-19-9. Analyses were done using the Kruskal-Wallis test, Mann-Whitney test, receiver operator characteristic, stepwise logistic regression and least squares support vector machines (LSSVM).

RESULTS

Plasma levels of IL-6, IL-8 and CA-125 were increased in all women with endometriosis and in those with minimal-mild endometriosis, compared with controls. In women with moderate-severe endometriosis, plasma levels of IL-6, IL-8 and CA-125, but also of hsCRP, were significantly higher than in controls. Using stepwise logistic regression, moderate-severe endometriosis was diagnosed with a sensitivity of 100% (specificity 84%) and minimal-mild endometriosis was detected with a sensitivity of 87% (specificity 71%) during the secretory phase. Using LSSVM analysis, minimal-mild endometriosis was diagnosed with a sensitivity of 94% (specificity 61%) during the secretory phase and with a sensitivity of 92% (specificity 63%) during the menstrual phase.

CONCLUSIONS

Advanced statistical analysis of a panel of six selected plasma biomarkers on samples obtained during the secretory phase or during menstruation allows the diagnosis of both minimal-mild and moderate-severe endometriosis with high sensitivity and clinically acceptable specificity.

摘要

背景

缺乏非侵入性诊断测试导致子宫内膜异位症症状出现与诊断之间存在较长的延迟。本研究旨在评估六种潜在血浆生物标志物联合用于诊断子宫内膜异位症的性能。

方法

本病例对照研究纳入了 294 名不孕妇女,其中 93 名妇女骨盆正常,201 名妇女患有子宫内膜异位症。我们测量了白细胞介素(IL)-6、IL-8、肿瘤坏死因子-α、高敏 C 反应蛋白(hsCRP)以及癌症抗原 CA-125 和 CA-19-9 的血浆浓度。使用 Kruskal-Wallis 检验、Mann-Whitney 检验、受试者工作特征曲线、逐步逻辑回归和最小二乘支持向量机(LSSVM)进行分析。

结果

所有患有子宫内膜异位症的妇女以及患有轻度子宫内膜异位症的妇女的血浆 IL-6、IL-8 和 CA-125 水平均升高,与对照组相比。在患有中重度子宫内膜异位症的妇女中,IL-6、IL-8 和 CA-125 以及 hsCRP 的血浆水平均显著高于对照组。使用逐步逻辑回归,中重度子宫内膜异位症的诊断敏感性为 100%(特异性 84%),轻度子宫内膜异位症的诊断敏感性为 87%(特异性 71%)在分泌期。使用 LSSVM 分析,在分泌期诊断轻度子宫内膜异位症的敏感性为 94%(特异性 61%),在月经期的敏感性为 92%(特异性 63%)。

结论

在分泌期或月经期采集的样本中对六种选定的血浆生物标志物进行高级统计分析,可以实现对轻度和中重度子宫内膜异位症的高敏感性和临床可接受的特异性诊断。

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