Perricos Alexandra, Wenzl René, Husslein Heinrich, Eiwegger Thomas, Gstoettner Manuela, Weinhaeusel Andreas, Beikircher Gabriel, Kuessel Lorenz
Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Pediatrics and Department of Immunology, University of Toronto; Toronto, ON M5G 1X8, Canada.
J Clin Med. 2020 Jun 26;9(6):2009. doi: 10.3390/jcm9062009.
Endometriosis appears to share certain cancer-related processes, such as cell attachment, invasion, proliferation and neovascularization, some of which can also be found in other healthy tissues. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we applied a multiplex oncology panel to search for specific biomarker signatures in the peritoneal fluid of women with endometriosis, women with deep-infiltrating endometriosis (DIE), as well as controls. In total, 84 patients were included in our study, 53 women with endometriosis and 31 controls. Ninety-two proteins were measured in prospectively collected peritoneal fluid (PF) samples, using the "Proseek Multiplex Oncology I Panel". We first compared patients with endometriosis versus controls, and in a second step, DIE versus endometriosis patients without DIE. Out of the 92 analyzed proteins, few showed significant differences between the groups. In patients with endometriosis, ICOS ligand, Endothelial growth factor, E-selectin, Receptor tyrosine-protein kinase erbB-2, Interleukin-6 receptor alpha, Vascular endothelial growth factor receptor 2, Fms-related tyrosine kinase 3 ligand, C-X-C motif chemokine 10, Epididymal secretory protein E4 and Folate receptor-alpha were decreased, while Interleukin-6 and Interleukin-8 were increased compared to controls. Looking at patients with DIE, we found Chemokine ligand 19, Stem cell factor, Vascular endothelial growth factor D, Interleukin-6 receptor alpha and Melanoma inhibitory activity to be increased compared to endometriosis patients without DIE. We have shown a distinct regulation of the immune response, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis in PF of patients with endometriosis compared to controls. The specific protein pattern in the PF of DIE patients provides new evidence that DIE represents a unique entity of extrauterine endometriosis with enhanced angiogenetic and pro-proliferative features.
子宫内膜异位症似乎与某些癌症相关过程有共同之处，如细胞黏附、侵袭、增殖和新血管形成，其中一些过程在其他健康组织中也能发现。为了更好地了解腹腔内环境的改变，同时认识到子宫内膜异位症与肿瘤形成过程之间已报道的相似性，我们应用了一个多重肿瘤检测板来寻找子宫内膜异位症患者、深部浸润型子宫内膜异位症（DIE）患者以及对照组女性腹膜液中的特定生物标志物特征。我们的研究共纳入了84例患者，其中53例为子宫内膜异位症患者，31例为对照组。使用“Proseek多重肿瘤检测板I”对前瞻性收集的腹膜液（PF）样本中的92种蛋白质进行了检测。我们首先比较了子宫内膜异位症患者与对照组，第二步比较了DIE患者与无DIE的子宫内膜异位症患者。在分析的92种蛋白质中，很少有蛋白质在两组之间显示出显著差异。与对照组相比，子宫内膜异位症患者中诱导共刺激分子配体（ICOS ligand）、内皮生长因子、E-选择素、受体酪氨酸蛋白激酶erbB-2、白细胞介素-6受体α、血管内皮生长因子受体2、Fms样酪氨酸激酶3配体、C-X-C基序趋化因子10、附睾分泌蛋白E4和叶酸受体α水平降低，而白细胞介素-6和白细胞介素-8水平升高。观察DIE患者，我们发现与无DIE的子宫内膜异位症患者相比，趋化因子配体19、干细胞因子、血管内皮生长因子D、白细胞介素-6受体α和黑色素瘤抑制活性升高。与对照组相比，我们发现子宫内膜异位症患者腹膜液中的免疫反应、血管生成、细胞增殖、细胞黏附及凋亡抑制存在明显的调控差异。DIE患者腹膜液中的特定蛋白质模式提供了新的证据，表明DIE代表了一种具有增强血管生成和促增殖特征的子宫外子宫内膜异位症的独特实体。
