Department of Gynecology and Obstetrics, Medical University of Vienna, Waehringer Guertel, Vienna, Austria.
Department of Pathology, Medical University of Vienna, Waehringer Guertel, Vienna, Austria.
Hum Reprod. 2017 Apr 1;32(4):770-779. doi: 10.1093/humrep/dex028.
Do cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis?
Altered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker.
Cell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes. Altered expression of VCAM-1 and ICAM-1 in women with endometriosis has been investigated previously; however, gene expression levels in tissues and protein levels in the serum have not been investigated in the same patients.
STUDY DESIGN SIZE, DURATION: We performed a prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent a laparoscopy for benign gynecological pathology in a university-based tertiary referral center for endometriosis. From a total of 138 women who were included in the study from July 2013 through September 2014, 97 had not received hormonal treatment for at least 3 months prior to recruitment and were included in the analysis; 49 (50.5%) of these women had endometriosis, and the 48 (49.5%) who did not have endometriosis served as a control group.
PARTICIPANTS/MATERIALS SETTING METHODS: During laparoscopy, tissue samples were obtained from ectopic and eutopic endometrium, and from normal pelvic peritoneum. In addition, serum samples were collected immediately before and 6-10 weeks after surgery. The mRNA levels of VCAM-1, ICAM-1 and epithelial cell adhesion molecule (EpCAM) were measured using quantitative real-time PCR, and serum protein levels of soluble VCAM-1 (sVCAM-1), ICAM-1 (sICAM-1) and EpCAM (sEpCAM) were measured using ELISA and correlated with endometriosis status.
The mRNA levels of both VCAM-1 and ICAM-1 were higher in ectopic endometriotic lesions than in eutopic endometrium (P < 0.001). Moreover, the mRNA levels of both VCAM-1 and ICAM-1 were higher in normal peritoneum samples obtained from women with endometriosis compared to those from controls (P = 0.038 and P = 0.009). The mRNA levels of VCAM-1 were also higher in the eutopic endometrium samples obtained from women with endometriosis compared to controls (P = 0.018). With respect to serum protein levels, compared to controls, the women with endometriosis had lower serum levels of sICAM-1 (P = 0.042) and higher levels of sVCAM-1 (P < 0.001). Our analysis revealed that the serum levels of sVCAM-1 were not affected by lesion entity, menstrual cycle phase or disease severity. An receiver operating characteristics curve, calculated to determine whether preoperative serum sVCAM-1 concentration can be used to predict endometriosis, found an AUC of 0.868 with 80% specificity and 84% sensitivity at a cutoff value of 370 pg/ml. This predictive performance can be further improved by calculation of the sVCAM-1/sICAM-1 ratio, leading to an AUC of 0.929 with 86.7% specificity and 90.3% sensitivity at a cutoff ratio value of 1.55.
Not applicable.
The relatively small sample size in the expression analyses is a possible limitation of this study.
Our findings could contribute to an improved understanding of the pathogenesis of endometriosis and the role of cell adhesion molecules. In addition, the results may lead to the development of new, non-invasive tools for diagnosing endometriosis. The ability to diagnose patients by measuring serum sVCAM-1 levels or the sVCAM-1/sICAM-1 ratio would have considerable clinical value.
STUDY FUNDING/COMPETING INTEREST(S): The Ingrid Flick Foundation (Grant no. FA751C0801), which played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.
细胞黏附分子在子宫内膜异位症中起作用吗？它们可以用作诊断子宫内膜异位症的生物标志物吗？
子宫内膜和腹膜中血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的表达改变可能在子宫内膜异位症中起关键作用，可溶性 VCAM-1/可溶性 ICAM-1 比值是一种很有前途的生物标志物。
细胞黏附分子是细胞表面蛋白，介导细胞黏附、炎症和免疫反应以及与癌症相关的生物学过程。以前已经研究了子宫内膜异位症患者中 VCAM-1 和 ICAM-1 的表达改变；然而，在同一患者中，尚未研究组织中的基因表达水平和血清中的蛋白水平。
研究设计/持续时间：我们在一家专门治疗子宫内膜异位症的大学附属三级转诊中心，对因良性妇科疾病行腹腔镜检查的患者进行了一项前瞻性、纵向研究（奥地利子宫内膜异位症标志物研究）。从 2013 年 7 月至 2014 年 9 月期间纳入研究的 138 名女性中，有 97 名女性在招募前至少 3 个月未接受激素治疗，她们被纳入分析；其中 49 名（50.5%）患有子宫内膜异位症，48 名（49.5%）没有子宫内膜异位症的女性作为对照组。
参与者/材料设置方法：在腹腔镜检查过程中，从异位和在位子宫内膜以及正常盆腔腹膜中获取组织样本。此外，在手术前和手术后 6-10 周采集血清样本。使用实时定量 PCR 测量 VCAM-1、ICAM-1 和上皮细胞黏附分子（EpCAM）的 mRNA 水平，使用 ELISA 测量可溶性 VCAM-1（sVCAM-1）、ICAM-1（sICAM-1）和 EpCAM（sEpCAM）的血清蛋白水平，并将其与子宫内膜异位症状态相关联。
异位子宫内膜异位症病变中的 VCAM-1 和 ICAM-1 的 mRNA 水平均高于在位子宫内膜（P < 0.001）。此外，子宫内膜异位症患者正常腹膜样本中的 VCAM-1 和 ICAM-1 的 mRNA 水平均高于对照组（P = 0.038 和 P = 0.009）。子宫内膜异位症患者在位子宫内膜样本中的 VCAM-1 mRNA 水平也高于对照组（P = 0.018）。关于血清蛋白水平，与对照组相比，子宫内膜异位症患者的血清 sICAM-1 水平较低（P = 0.042），sVCAM-1 水平较高（P < 0.001）。我们的分析表明，术前血清 sVCAM-1 浓度不能预测疾病严重程度或月经周期阶段。计算受试者工作特征曲线以确定术前血清 sVCAM-1 浓度是否可用于预测子宫内膜异位症，发现 AUC 为 0.868，特异性为 80%，敏感性为 84%，截断值为 370 pg/ml。通过计算 sVCAM-1/sICAM-1 比值，可以进一步提高这种预测性能，导致 AUC 为 0.929，特异性为 86.7%，敏感性为 90.3%，截断比值为 1.55。
不适用。
局限性/谨慎的原因：在表达分析中，样本量较小可能是该研究的一个局限性。
我们的发现可能有助于更好地理解子宫内膜异位症的发病机制和细胞黏附分子的作用。此外，这些结果可能导致开发新的、非侵入性的子宫内膜异位症诊断工具。通过测量血清 sVCAM-1 水平或 sVCAM-1/sICAM-1 比值来诊断患者将具有重要的临床价值。
研究资金/利益冲突：Ingrid Flick 基金会（资助号 FA751C0801）在研究设计、数据收集和分析、决策发布或手稿准备过程中没有发挥作用。作者没有利益冲突。
