Potential of testis-derived circular RNAs in seminal plasma to predict the outcome of microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia
Potential of testis-derived circular RNAs in seminal plasma to predict the outcome of microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia
复制标题
精浆中睾丸来源的环状 RNA 预测特发性非梗阻性无精子症患者显微切割睾丸精子提取结果的潜力
DOI：
10.1093/humrep/deab196
复制
发表时间：
2021-09-04
影响因子：
6.1
通讯作者：
Song, Ninghong
中科院分区：
文献类型：
--
作者：
Ji, Chengjian;Wang, Yichun;Song, Ninghong
研究问题：精血浆中睾丸源性环状rna （circRNAs）是否有潜力作为生物标志物，预测特发性非阻塞性无精子症（NOA）患者显微解剖睾丸精子提取（micro-TESE）的结果？结论：精浆中睾丸来源的环状rna确实可以用于预测特发性NOA患者的微tese结果。已知情况：Micro-TESE是一种从特发性NOA患者获得精子样本的有效方法。然而，在这类患者中，其成功率仅为40-50%。研究设计、规模、持续时间：6例具有不同显微tese结果的特发性NOA患者被纳入发现队列。他们的睾丸组织用于提取和测序环状rna。选择表达水平差异最大的5个circrna进行进一步验证。参与者/材料、环境、方法：52例特发性NOA患者被纳入验证队列。收集52例特发性NOA患者术前精浆及25例术中睾丸组织，根据显微tese结果分为“成功”组和“失败”组。采用实时定量聚合酶链反应验证两组患者睾丸组织和精浆中所选环状rna表达水平的差异。主要结果和CHANCE的作用：无论是在精浆还是睾丸组织水平，成功组和失败组之间三种circRNAs （hsa_circ_0000277、hsa_circ_0060394和hsa_circ_0007773）的表达水平差异与测序结果一致。AUC的诊断接受者工作曲线（ROC）分析显示，精浆中这些环状rna在预测微tese结果方面具有出色的诊断性能（AUC值分别为0.920、0.928和0.891）。在最小绝对收缩和选择算子（LASSO）逻辑回归的基础上，将三个circrna组合起来构建新的预测模型。模型的诊断ROC曲线分析显示AUC值为0.958。使用三个正常精子志愿者样本，在室温下48小时后，这些环状rna在精浆中的表达水平保持稳定。大规模数据：没有。局限性和谨慎的原因：这是一项病例相对较少的单中心回顾性研究。这些环状rna的功能以及它们与精子发生的关系尚未确定。研究结果的更广泛含义：精血浆中睾丸来源的环状rna可以反映睾丸的微环境，可以作为可靠的生物标志物来筛选可能适合微tese的特发性NOA患者。
STUDY QUESTION: Do testis-derived circular RNAs (circRNAs) in seminal plasma have potential as biomarkers to predict the outcome of microdissection testicular sperm extraction (micro-TESE) in patients with idiopathic non-obstructive azoospermia (NOA)?SUMMARY ANSWER: Testis-derived circRNAs in the seminal plasma can indeed be used for predicting the outcome of micro-TESE in patients with idiopathic NOA.WHAT IS KNOWN ALREADY: Micro-TESE is an effective method to obtain sperm samples from patients with idiopathic NOA. However, its success rate is only 40-50% in such patients.STUDY DESIGN, SIZE, DURATION: Six idiopathic NOA patients with different micro-TESE results were included as the discovery cohort. Their testicular tissues were used for extracting and sequencing circRNAs. Five circRNAs with the most significantly different expression levels were selected for further verification.PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-two patients with idiopathic NOA were included as the validation cohort. Preoperative seminal plasma samples of 52 patients with idiopathic NOA and 25 intraoperative testicular tissues were collected and divided into 'success' and 'failure' groups according to the results of micro-TESE. Quantitative real-time polymerase chain reaction was performed to verify differences in the expression levels of the selected circRNAs between the two groups in the testicular tissues and seminal plasma.MAIN RESULTS AND THE ROLE OF CHANCE: Whether at the seminal plasma or testicular tissue level, the differences in the expression levels of the three circRNAs (hsa_circ_0000277, hsa_circ_0060394 and hsa_circ_0007773) between the success and failure groups were consistent with the sequencing results. A diagnostic receiver operating curve (ROC) analysis of the AUC indicated excellent diagnostic performance of these circRNAs in seminal plasma in predicting the outcome of micro-TESE (AUC values: 0.920, 0.928 and 0.891, respectively). On the basis of least absolute shrinkage and selection operator (LASSO) logistic regression, the three circRNAs were combined to construct a new prediction model. The diagnostic ROC curve analysis of the model showed an AUC value of 0.958. The expression levels of these circRNAs in seminal plasma using three normospermic volunteer samples remained stable after 48 h at room temperature.LARGE SCALE DATA: NA.LIMITATIONS, REASONS FOR CAUTION: This was a single-center retrospective study with relatively few cases. The functions of these circRNAs, as well as their relationship with spermatogenesis, have not yet been established.WIDER IMPLICATIONS OF THE FINDINGS: Testis-derived circRNAs in seminal plasma can reflect the microenvironment of the testis and can be used as reliable biomarkers to screen patients with idiopathic NOA who might be suitable for micro-TESE.