Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
J Clin Endocrinol Metab. 2019 Jun 1;104(6):1999-2022. doi: 10.1210/jc.2018-01464.
Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers; however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts.
Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy.
Two university-based, public hospitals and a private gynecology practice in Australia.
Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119).
Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively.
Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups' findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
尽管广泛搜索了新型非侵入性诊断方法，但腹腔镜检查仍然是子宫内膜异位症的参考测试。循环 miRNA 被认为是子宫内膜异位症的生物标志物；然而，在不同的研究中，miRNA 种类及其诊断准确性存在差异，并且尚未在独立队列中得到验证。
确定子宫内膜异位症特异性血浆 miRNA 并确定其诊断测试准确性。
澳大利亚的两家基于大学的公立医院和一家私立妇科诊所。
四个阶段：（i）探索阶段。在患有子宫内膜异位症和无症状对照的女性中评估血浆 miRNA 月经周期波动（n = 16）。（ii）生物标志物发现。在（a）患有子宫内膜异位症的女性和无症状对照（n = 16）以及（b）患有和不患有手术定义的子宫内膜异位症的女性（n = 20）中确定子宫内膜异位症特异性血浆 miRNA。（iii）生物标志物选择。在手术定义的选择队列（n = 78）中选择具有最佳诊断潜力的血浆 miRNA。（iv）生物标志物验证。在独立的手术定义验证队列（n = 119）中计算这些 miRNA 的诊断测试准确性。
在患有子宫内膜异位症的女性中，有 49 种 miRNA 表达差异。在选择队列中，有 9 种 miRNA 保持失调，但只有 3 种（miR-155、miR574-3p 和 miR139-3p）在验证队列中保持失调。这三种 miRNA 的组合具有 83%的敏感性和 51%的特异性。
血浆 miRNA 作为子宫内膜异位症的诊断测试或筛查工具表现出中等的敏感性和特异性。其他组的发现未被复制，与我们的结果相差很大。循环 miRNA 具有诊断潜力，但需要严格、标准化的方法学方法来开发临床适用的工具。
