Department of Gynecology and Obstetrics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Biol Reprod. 2013 May 16;88(5):122. doi: 10.1095/biolreprod.112.103598. Print 2013 May.
Considerable effort has been invested in searching for less invasive methods of diagnosing endometriosis. Previous studies have indicated altered levels of the CALD1 gene (encoding the protein caldesmon) in endometriosis. The aims of our study were to investigate whether average CALD1 expression and caldesmon protein levels are differentially altered in the endometrium and endometriotic lesions and to evaluate the performance of the CALD1 gene and caldesmon protein as potential biomarkers for endometriosis. Paired biopsies of endometrial tissue (eutopic endometrium) and endometriotic lesions (ectopic endometrium) were obtained from patients with endometriosis to evaluate CALD1 gene expression and caldesmon protein levels by real-time PCR and Western blot analysis, respectively. In addition, immunostaining for caldesmon to determine cellular localization was also performed. Endometrium from women without endometriosis was used as a control. Increased CALD1 expression and caldesmon levels were detected in the endometriotic lesions. The electrophoretic profile of caldesmon by Western blot analysis was clearly different between the control group (endometrium of women without endometriosis) and the group of women with endometriosis (eutopic endometrium and endometriotic lesions). Caldesmon expression as determined by immunostaining showed no variation among the cell types in endometriotic lesions and eutopic endometrium. Stromal cells marked positively in eutopic endometrium from control patients and in the endometriotic lesions. The presence of caldesmon in the endometrium of patients with and without endometriosis permitted diagnoses with 95% sensitivity (specificity 100%) and 100% sensitivity (specificity 100%) for the disease and for minimal to mild endometriosis in the proliferative phase of the menstrual cycle, respectively. In the secretory phase, minimal to mild endometriosis was detected with 90% sensitivity and 93.3% specificity. Caldesmon is a possible predictor of endometrial dysregulation in patients with endometriosis. A potential limitation of our study is the fact that other endometrial diseases were not excluded, and therefore prospective studies are needed to confirm the potential of caldesmon as a biomarker exclusively for endometriosis.
人们投入了大量精力来寻找诊断子宫内膜异位症的非侵入性方法。先前的研究表明,CALD1 基因(编码钙调蛋白)在子宫内膜异位症中存在改变。我们的研究目的是探讨 CALD1 表达和钙调蛋白水平在子宫内膜和子宫内膜异位病变中的改变是否存在差异,并评估 CALD1 基因和钙调蛋白作为子宫内膜异位症潜在生物标志物的性能。通过实时 PCR 和 Western blot 分析分别检测子宫内膜异位症患者的子宫内膜(在位内膜)和子宫内膜异位病变(异位内膜)的配对活检标本中的 CALD1 基因表达和钙调蛋白水平。此外,还进行了钙调蛋白的免疫染色以确定细胞定位。将没有子宫内膜异位症的女性的子宫内膜作为对照。结果显示,在子宫内膜异位病变中检测到 CALD1 表达增加和钙调蛋白水平升高。Western blot 分析中钙调蛋白的电泳谱在对照组(无子宫内膜异位症的女性的子宫内膜)和子宫内膜异位症组(在位内膜和子宫内膜异位病变)之间明显不同。免疫染色确定的钙调蛋白表达在子宫内膜异位病变和在位内膜的细胞类型之间没有变化。在对照组患者的在位内膜和子宫内膜异位病变中,基质细胞呈阳性标记。在有和没有子宫内膜异位症的患者的子宫内膜中均存在钙调蛋白,这使得疾病的诊断具有 95%的敏感性(特异性 100%)和 100%的敏感性(特异性 100%),并且在月经周期的增殖期分别可检测到轻度至轻度子宫内膜异位症。在分泌期,可检测到轻度至轻度子宫内膜异位症,其敏感性为 90%,特异性为 93.3%。钙调蛋白可能是子宫内膜异位症患者子宫内膜失调的预测因子。我们研究的一个潜在局限性是未排除其他子宫内膜疾病,因此需要进行前瞻性研究以确认钙调蛋白作为子宫内膜异位症的生物标志物的潜力。