Sampling of bile juice during endoscopic retrograde cholangiopancreatography (ERCP) has potential benefit of being amenable to the identification of novel biomarkers in liquid biopsy. This study reports the results of a global investigation of exosomal microRNAs (miRNAs) in bile to identify potential biomarkers for biliary tract cancers (BTCs). Eighty-eight bile samples collected during ERCP (45 BTC and 43 noncancer control samples) were enrolled in this study. Eleven BTC samples and nine control samples were assigned as the discovery set. Exosomes in bile and serum samples were collected using a glass membrane column with size-controlled macroporous glass (MPG), and exosomal miRNA expression profiles were evaluated using comprehensive miRNA microarray analysis (3D-Gene). For validation, exosomal miRNA in the bile samples of 34 BTCs and 34 controls were comprehensively evaluated using 3D-Gene. In the discovery set, eight exosomal miRNAs in bile were identified as significant aberrant expression markers, while no miRNA with aberrant expression in serum was identified. In a comparison of the discovery and validation sets, miR-451a and miR-3619-3p were identified as reproducible upregulated markers, and the combination of the two bile miRNAs showed an excellent area under the curve (0.819) value for diagnosing BTCs. In addition, high miR-3619-3p expression in bile reflects poorer prognosis of BTCs (hazard ratio = 2.89). The MPG-extracted exosomal miRNAs in bile aspirated during ERCP provide a convenient new approach for diagnosing biliary diseases. Bile-derived miRNA analysis with miR-451a and miR-3619-3p represents a potentially valuable diagnostic strategy for identifying BTCs as well as a predictive indicator of BTC prognosis.

中文翻译：

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胆源性外泌体 microRNA 作为胆道癌新型诊断和预后生物标志物的临床影响

内窥镜逆行胰胆管造影术 (ERCP) 期间的胆汁取样具有潜在的好处，可以在液体活检中识别新的生物标志物。本研究报告了胆汁中外泌体 microRNA (miRNA) 的全球调查结果，以确定胆道癌 (BTC) 的潜在生物标志物。在 ERCP 期间收集的 88 个胆汁样本（45 个 BTC 和 43 个非癌症对照样本）被纳入本研究。十一个 BTC 样本和九个对照样本被指定为发现集。使用尺寸可控的大孔玻璃 (MPG) 玻璃膜柱收集胆汁和血清样品中的外泌体，并使用综合 miRNA 微阵列分析（3D-Gene）评估外泌体 miRNA 表达谱。为了验证，使用 3D-Gene 对 34 个 BTC 和 34 个对照的胆汁样本中的外泌体 miRNA 进行了全面评估。在发现集中，胆汁中的 8 个外泌体 miRNA 被鉴定为显着的异常表达标记，而血清中未鉴定出具有异常表达的 miRNA。在发现集和验证集的比较中，miR-451a 和 miR-3619-3p 被确定为可重现的上调标记，并且两种胆汁 miRNA 的组合显示出用于诊断 BTC 的出色曲线下面积 (0.819) 值。此外，胆汁中 miR-3619-3p 的高表达反映了 BTC 的预后较差（风险比 = 2.89）。在 ERCP 期间抽吸的胆汁中 MPG 提取的外泌体 miRNA 为诊断胆道疾病提供了一种方便的新方法。