Meijer Laura L, Puik Jisce R, Le Large Tessa Y S, Heger Michal, Dijk Frederike, Funel Niccola, Wurdinger Thomas, Garajová Ingrid, van Grieken Nicole C T, van de Wiel Mark A, Giovannetti Elisa, Kazemier Geert
Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands.
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands.
Cancers (Basel). 2019 Aug 15;11(8):1181. doi: 10.3390/cancers11081181.
Accurate diagnosis of pancreatic head lesions remains challenging as no minimally invasive biomarkers are available to discriminate distal cholangiocarcinoma (CCA) from pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to identify specific circulating microRNAs (miRNAs) to diagnose distal CCA. In the discovery phase, PCR profiling of 752 miRNAs was performed on fourteen patients with distal CCA and age- and sex-matched healthy controls. Candidate miRNAs were selected for evaluation and validation by RT-qPCR in an independent cohort of distal CCA ( = 24), healthy controls ( = 32), benign diseases ( = 20), and PDAC ( = 24). The optimal diagnostic combination of miRNAs was determined by multivariate logistic regression analysis and evaluated by ROC curves with AUC values. The discovery phase revealed 19 significantly dysregulated miRNAs, of which six were validated in the evaluation phase. The validation phase confirmed downregulated miR-16 in patients with distal CCA compared to benign disease or PDAC ( = 0.048 and = 0.012), while miR-877 was significantly upregulated ( = 0.003 and = 0.006). This two-miRNA panel was validated as a CCA-specific profile, discriminating distal CCA from benign disease (AUC = 0.90) and from PDAC (AUC = 0.88). In conclusion, the present study identified a two-miRNA panel of downregulated miR-16 and upregulated miR-877 with promising capability to diagnose patients with distal CCA.
由于没有微创生物标志物可用于区分远端胆管癌（CCA）和胰腺导管腺癌（PDAC），胰腺头部病变的准确诊断仍然具有挑战性。本研究的目的是鉴定用于诊断远端CCA的特异性循环微小RNA（miRNA）。在发现阶段，对14例远端CCA患者以及年龄和性别匹配的健康对照进行了752种miRNA的PCR分析。通过RT-qPCR在一个独立的远端CCA队列（n = 24）、健康对照（n = 32）、良性疾病（n = 20）和PDAC（n = 24）中选择候选miRNA进行评估和验证。通过多变量逻辑回归分析确定miRNA的最佳诊断组合，并通过具有AUC值的ROC曲线进行评估。发现阶段揭示了19种显著失调的miRNA，其中6种在评估阶段得到验证。验证阶段证实，与良性疾病或PDAC相比，远端CCA患者中miR-16下调（P = 0.048和P = 0.012），而miR-877显著上调（P = 0.003和P = 0.006）。这两种miRNA组合被验证为CCA特异性谱，可将远端CCA与良性疾病（AUC = 0.90）和PDAC（AUC = 0.88）区分开来。总之，本研究鉴定了一种由下调的miR-16和上调的miR-877组成的双miRNA组合，具有诊断远端CCA患者的良好潜力。
