Kocbek Vida, Vouk Katja, Bersinger Nick A, Mueller Michael D, Lanišnik Rižner Tea
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Endometriosis Centre, Department of Obstetrics and Gynaecology, Inselspital, University of Berne, Berne, Switzerland.
J Mol Diagn. 2015 May;17(3):325-34. doi: 10.1016/j.jmoldx.2015.01.006. Epub 2015 Mar 20.
Endometriosis is a gynecologic disease that is characterized by nonspecific symptoms and invasive diagnostics. To date, there is no adequate noninvasive method for the diagnosis of endometriosis. Although more than 100 potential biomarkers have been investigated in blood and/or peritoneal fluid, none of these has proven useful in clinical practice. The aim to find a suitable panel of biomarkers that would allow noninvasive diagnosis thus remains of interest. We evaluated the concentrations of 16 cytokines and other secretory proteins in serum and peritoneal fluid of 58 women with ovarian endometriosis (cases) and 40 healthy women undergoing sterilization or patients with benign ovarian cysts (controls) using multiplexed double fluorescence-based immunometric assay platform and enzyme-linked immunosorbent assay. Significantly higher concentrations of glycodelin-A were shown in serum, and significantly higher levels of glycodelin-A, IL-6, and IL-8, and lower levels of leptin were measured in the peritoneal fluid of cases versus controls. In serum, the best performance was shown by models that included the ratio of leptin/glycodelin-A and the ratio of ficolin 2/glycodelin-A, whereas in the peritoneal fluid the best models included the ratio of biglycan/leptin, regulated on activation normal T-cell expressed and secreted/IL-6 and ficolin-2/glycodelin-A, and IL-8 per milligram of total protein, all in combination with age. The models using serum and peritoneal fluid distinguished between ovarian endometriosis patients and controls regardless of the menstrual cycle phase with relatively high sensitivity (72.5% to 84.2%), specificity (78.4% to 91.2%), and area under the curve (0.85 to 0.90).
子宫内膜异位症是一种妇科疾病，其特征为非特异性症状和侵入性诊断方法。迄今为止，尚无足够的非侵入性方法用于诊断子宫内膜异位症。尽管已经在血液和/或腹水中研究了100多种潜在生物标志物，但这些标志物在临床实践中均未被证明有用。因此，寻找一组能够实现非侵入性诊断的合适生物标志物的目标仍然备受关注。我们使用基于多重双荧光的免疫分析平台和酶联免疫吸附测定法，评估了58例卵巢子宫内膜异位症患者（病例组）和40例接受绝育手术的健康女性或卵巢良性囊肿患者（对照组）血清和腹水中16种细胞因子及其他分泌蛋白的浓度。结果显示，病例组血清中糖蛋白A的浓度显著更高，腹水中糖蛋白A、白细胞介素-6和白细胞介素-8的水平显著更高，而瘦素水平更低。在血清中，包含瘦素/糖蛋白A比值和纤维胶凝蛋白2/糖蛋白A比值的模型表现最佳；而在腹水中，最佳模型包括双聚糖/瘦素比值、活化正常T细胞表达和分泌因子/白细胞介素-6、纤维胶凝蛋白-2/糖蛋白A以及每毫克总蛋白中的白细胞介素-8，所有这些均与年龄相结合。使用血清和腹水的模型能够区分卵巢子宫内膜异位症患者和对照组，无论月经周期处于何阶段，具有相对较高的敏感性（72.5%至84.2%）、特异性（78.4%至91.2%）和曲线下面积（0.85至0.90）。
