先前与女性雄激素过量相关的循环miRNA可能用作多囊卵巢综合征(PCOS)的诊断生物标志物。
基于循环miR-142-3p和miR-598-3p表达的模型在有和没有PCOS的女性中显示出良好的区别性。特别是与腰臀比(WHR)和循环LH与FSH(LH/FSH)比值等易于获得的测量值结合使用时。
标志缺乏标准化,方法,和用于确定诊断标准存在的阈值(高雄激素血症,排卵障碍,和多囊卵巢形态学)使PCOS的诊断复杂化。某些生物标志物可能有助于这样的诊断。我们进行了一项验证研究,以检查与我们的研究小组先前进行的一项小型试点研究中与该综合征相关的几种miRNA对PCOS的诊断准确性。
这是一项涉及140名绝经前妇女的诊断测试研究。
我们在研究中纳入了71名PCOS女性和69名健康对照女性。两组均选择为在体重指数方面相似。我们使用miRCURYLNA™通用RTmicroRNAPCR来分析在我们小组先前进行的较小的试点研究中显示与PCOS最强关联的五种miRNA。我们使用接收器工作特征(ROC)曲线分析研究了诊断准确性。
只有两个miRNAs的表达,miR-142-3p和miR-598-3p,在研究的五个人中,PCOS女性和非高雄激素对照组之间存在差异。这些循环miRNA的组合的诊断准确性良好(ROC曲线下面积(AUC)0.801;95%CI:0.72-0.88),并且在添加WHR时进一步提高(AUC0.834,95%CI:0.756-0.912),LH/FSH比率(AUC=0.869,95%CI:0.804-0.934)或两者(AUC=0.895,95%CI:0.835-0.954)。我们通过为这些变量选择不同的阈值来开发几个模型,这些变量有利于敏感性或特异性,阳性和阴性预测值高达88%或85%,分别。
这里包括的患者具有经典的PCOS表型,由高雄激素血症和排卵功能障碍组成;因此,目前的结果可能不适用于缺乏雄激素过量的温和表型。
如果在针对不同人群和PCOS表型的大型研究中得到证实,这些生物标志物可能有助于简化这一普遍综合征的临床诊断.
这项研究由卡洛斯三世研究所资助,西班牙科学与创新部(授予PI15/01686,PIE16/00050,PI18/01122和PI21/00116),并由欧洲区域发展基金共同资助“一种制造欧洲的方式”。研究中心(CIBERDEM)和RamónyCajaldeInvestigaciónSanitaria(IRYCIS)也是SaludCarlosIII研究所的倡议。作者没有竞争利益可披露。
不适用。
Circulating miRNAs previously associated with androgen excess in women might be used as diagnostic biomarkers for polycystic ovary syndrome (PCOS).
Models based on circulating miR-142-3p and miR-598-3p expression show good discrimination among women with and without PCOS, particularly when coupled with easily available measurements such as waist-to-hip ratio (WHR) and circulating LH-to-FSH (LH/FSH) ratios.
The lack of standardization of the signs, methods, and threshold values used to establish the presence of the diagnostic criteria (hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology) complicates the diagnosis of PCOS. Certain biomarkers may help with such a diagnosis. We conducted a validation study to check the diagnostic accuracy for PCOS of several miRNAs that were associated with the syndrome in a small pilot study that had been previously carried out by our research group.
This was a diagnostic test study involving 140 premenopausal women.
We included 71 women with PCOS and 69 healthy control women in the study. Both groups were selected as to be similar in terms of body mass index. We used miRCURY LNA™ Universal RT microRNA PCR to analyse the five miRNAs that had shown the strongest associations with PCOS in a much smaller pilot study previously conducted by our group. We studied diagnostic accuracy using receiver operating characteristics (ROC) curve analysis.
Only the expression of two miRNAs, miR-142-3p and miR-598-3p, of the five studied, was different between the women with PCOS and the non-hyperandrogenic controls. The diagnostic accuracy of the combination of these circulating miRNAs was good (area under the ROC curve (AUC) 0.801; 95% CI: 0.72-0.88) and was further improved when adding WHR (AUC 0.834, 95% CI: 0.756-0.912), LH/FSH ratio (AUC = 0.869, 95% CI: 0.804-0.934) or both (AUC = 0.895, 95% CI: 0.835-0.954). We developed several models by selecting different threshold values for these variables favouring either sensitivity or specificity, with positive and negative predictive values as high as 88% or 85%, respectively.
Patients included here had the classic PCOS phenotype, consisting of hyperandrogenism and ovulatory dysfunction; hence, the present results might not apply to milder phenotypes lacking androgen excess.
If confirmed in larger studies addressing different populations and PCOS phenotypes, these biomarkers may be useful to simplify the clinical diagnosis of this prevalent syndrome.
This research was funded by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (grants PI15/01686, PIE16/00050, PI18/01122 & PI21/00116) and co-funded by European Regional Development Fund \'A way to make Europe\'. Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) are also initiatives of the Instituto de Salud Carlos III. The authors have no competing interests to disclose.
N/A.