Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea; Departments of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea.
Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Korea.
Hepatobiliary Pancreat Dis Int. 2020 Feb;19(1):41-50. doi: 10.1016/j.hbpd.2019.10.009. Epub 2019 Nov 8.
Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples that are differentially expressed between benign biliary disease (BBD) and CCA.
Bile samples from 106 patients with obstructive biliary disease were allocated consecutively to a discovery set (10 patients with BBD and 11 with CCA) and then a validation set (48 patients with BBD and 37 with CCA). An miRNA microarray platform was used to screen 1209 miRNAs in the discovery set. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results in the discovery and validation sets. In addition, the levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were determined from patient serum samples.
Microarray profiling showed that miR-30d-5p and miR-92a-3p were significantly upregulated in bile from the CCA group compared with those from the BBD group. qRT-PCR results indicated that the expression levels of miR-30d-5p and of miR-92a-3p were significantly upregulated in the CCA group compared to the BBD group, validating the miRNA microarray results. Pathway analysis suggested that putative target genes of miR-30d-5p and of miR-92a-3p were involved in CCA-associated signalling pathways, such as Hippo, Wnt, p53, MAPK, and EGFR. Receiver operating curve analysis revealed that the areas under the curve for bile miR-30d-5p, miR-92a-3p, serum CA19-9, and CEA were 0.730, 0.652, 0.675, and 0.603, respectively, and bile miR-30d-5p showed the best diagnostic performance with a sensitivity of 81.1% and a specificity of 60.5%.
The levels of extracellular miR-30d-5p and miR-92a-3p in bile were significantly higher in patients with CCA than those in patients with BBD. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p are potential biomarkers for discriminating CCA from BBD.
胆管癌（CCA）来源于胆管细胞，因此胆汁是 CCA 潜在的丰富生物标志物来源。本研究旨在鉴定和验证胆汁样本中在良性胆道疾病（BBD）和 CCA 之间存在差异表达的 microRNAs（miRNAs）。
连续分配 106 例梗阻性胆道疾病患者的胆汁样本至发现集（10 例 BBD 和 11 例 CCA）和验证集（48 例 BBD 和 37 例 CCA）。使用 miRNA 微阵列平台筛选发现集中的 1209 个 miRNAs。定量实时逆转录聚合酶链反应（qRT-PCR）用于验证发现集和验证集中的分析结果。此外，还从患者血清样本中测定了癌抗原 19-9（CA19-9）和癌胚抗原（CEA）的水平。
微阵列分析显示，与 BBD 组相比，CCA 组胆汁中的 miR-30d-5p 和 miR-92a-3p 显著上调。qRT-PCR 结果表明，与 BBD 组相比，CCA 组中 miR-30d-5p 和 miR-92a-3p 的表达水平显著上调，验证了 miRNA 微阵列结果。途径分析表明，miR-30d-5p 和 miR-92a-3p 的假定靶基因参与了与 CCA 相关的信号通路，如 Hippo、Wnt、p53、MAPK 和 EGFR。受试者工作特征曲线分析显示，胆汁 miR-30d-5p、miR-92a-3p、血清 CA19-9 和 CEA 的曲线下面积分别为 0.730、0.652、0.675 和 0.603，并且胆汁 miR-30d-5p 具有最佳的诊断性能，其灵敏度为 81.1%，特异性为 60.5%。
与 BBD 患者相比，CCA 患者胆汁中细胞外 miR-30d-5p 和 miR-92a-3p 的水平显著升高。来源于胆汁的循环细胞外 miR-30d-5p 和 miR-92a-3p 可能是鉴别 CCA 与 BBD 的潜在生物标志物。
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