Background: Endometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment.
Methods: A total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions.
Results: Among 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752-0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571-0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network.
Conclusions: This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.
环状RNA可作为鉴定卵巢子宫内膜异位症的一种新型 生物标志物摘要背景: 子宫内膜异位症是一种极具挑战性的妇科疾病，主要症状为痛经和不孕。目前，它的发病机制尚不清楚，也没有有效的标记物和治疗办法。本研究的主要目的是分析卵巢子宫内膜异位症患者在位内膜中环状RNAs（circRNAs）的表达；探索子宫内膜异位症的潜在发病机制，为临床诊断和治疗提供依据。 方法: 收集2016年5月1日至2016年12月31日北京协和医院的标本共63例，其中，卵巢子宫内膜异位症患者的在位内膜41例，对照组内膜22例。每组各4例标本用于circRNAs的芯片分析，从中选取4个上调明显的circRNAs用于大样本qRT-PCR验证。之后采用生物信息学分析预测验证出的环状RNA的靶向miRNA及circRNA-miRNAs-mRNAs作用网络。 结果: circRNAs芯片结果显示卵巢子宫内膜异位症患者的在位内膜较对照组内膜相比，共88个差异表达的circRNAs，其中11个上调、77个下调。qRT-PCR验证结果显示circ_0004712和circ_0002198与芯片结果一致，其受试者特征曲线下的面积分别为0.704 (95%CI: 0.571 - 0.837; P = 0.008)、0.846 (95%CI: 0.752 - 0.939; P < 0.001)。根据靶基因预测，我们还描述了circ_0004712、circ_0002198与其主要靶miRNAs的相互作用，同时构建了一个circRNA-miRNA-mRNA作用网络。 结论: 本研究发现circRNA在在位内膜及对照组内膜之间的确存在差异，这表明circRNAs在卵巢子宫内膜异位症的发病过程中可能起着关键作用。此外，circ_0004712及circ_0002198可能成为诊断卵巢子宫内膜异位症的新型生物标记物。.
Keywords: Circular RNA; Endometriosis; Microarray; mRNA; miRNA.