Identification and validation of novel serum markers for early diagnosis of endometriosis
Identification and validation of novel serum markers for early diagnosis of endometriosis
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DOI：
10.1093/humrep/der410
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发表时间：
2012-02-01
影响因子：
6.1
通讯作者：
Khole, V.
中科院分区：
文献类型：
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作者：
Gajbhiye, R.;Sonawani, A.;Khole, V.
背景：目前迫切需要对子宫内膜异位症进行无创性诊断，以防止出现症状和诊断之间的长时间延迟。因此，迫切需要一种同时具有高度敏感性和特异性的生物标记物。在这里，我们描述了使用蛋白质组学方法从子宫内膜异位症患者和健康对照组的血清中寻找潜在的新的子宫内膜抗原，并评价了用于非侵入性诊断子宫内膜异位症的生物标志物。方法：采用一种横断面研究方法，使用1D和2D蛋白质印迹技术在早期子宫内膜异位症(n=17)、晚期子宫内膜异位症(n=23)和非子宫内膜异位症(n=30)的妇女中识别特定的子宫内膜抗原。用基质辅助激光解吸/电离飞行时间/质谱仪分析5个免疫反应点，结合吉祥物分析。建立针对特定表位的ELISA，并在包括早期子宫内膜异位症(18例)、晚期子宫内膜异位症(32例)和非子宫内膜异位症(27例)的独立队列中估计自身抗体效价。结果：2D蛋白质印迹分析鉴定出3种子宫内膜抗原，即原肌球蛋白3(TPM3)、口腔素样蛋白2(SLP2)和原肌球蛋白3(TMOD3)。子宫内膜异位症患者血清中针对TPM3、SLP2和TMOD3免疫优势区表位的抗体水平显著高于对照组。血清抗TPM3a、抗TPM3c、抗TPM3d、抗SLP2a、抗SLP2c、抗TMOD3b、抗TMOD3b、抗TMOD3c、抗TMOD3d、抗TMOD3d的敏感性和特异性分别为61%、93%、44%、93%、78%、96%、78%、96%。结论：血清抗TPM3a、抗TPM3c、抗TPM3d、抗SLP2a、抗SLP2c、抗TMOD3b、抗TMOD3b、抗TMOD3c、抗TMOD3d可作为子宫内膜异位症早期诊断的新指标。
BACKGROUND: Non-invasive diagnosis of endometriosis is urgently required to prevent the long delay between the onset of symptoms and diagnosis. A biomarker that possesses both high sensitivity and specificity is greatly required. Here, we describe the use of a proteomic approach to identify potential novel endometrial antigens using sera from endometriosis patients and healthy controls, with evaluation of biomarkers for non-invasive diagnosis of endometriosis.METHODS: A cross-sectional study was conducted to identify specific endometrial antigens using 1D and 2D western blots in women with early endometriosis (n = 17), advanced endometriosis (n = 23) and without endometriosis (n = 30). Five immunoreactive spots were analyzed using matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry with MASCOT analysis. ELISAs were established for specific epitopes and autoantibody titres were estimated in an independent cohort comprising women with early endometriosis (n = 18), advanced endometriosis (n = 32) and without endometriosis (n = 27) for validation.RESULTS: The 2D western blot analysis resulted in the identification of three endometrial antigens, tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3). Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3, SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls. Sensitivity and specificity of serum anti-TPM3a-autoAb (61%, 93%), anti-TPM3c-autoAb (44%, 93%), anti-TPM3d-autoAb (78%, 89%), anti-SLP2a-autoAb (50%, 96%), anti-SLP2c-autoAb (61%, 93%), anti-TMOD3b-autoAb (61%, 96%), serum anti-TMOD3c-autoAb (78%, 93%) and anti-TMOD3d-autoAb (78%, 96%) were better than those of serum CA125 levels (21%, 89%) in the detection of early stages of endometriosis.CONCLUSIONS: Serum anti-TPM3a-autoAb, anti-TPM3c-autoAb, anti-TPM3d-autoAb, anti-SLP2a-autoAb, anti-SLP2c-autoAb, anti-TMOD3b-autoAb, anti-TMOD3c-autoAb and anti-TMOD3d-autoAb could be new markers for the early diagnosis of endometriosis.