医学
内镜逆行胰胆管造影术
胃肠病学
内科学
小RNA
队列
经皮肝穿刺胆管造影
胰腺癌
黄疸
病理
癌症
肿瘤科
胆管造影
胰腺炎
基因
生物
生物化学
作者
Daniel Liu,Jisce R. Puik,Morten T. Venø,Mireia Mato Prado,E. Douglas Rees,Bhavik Y. Patel,Nabeel Merali,Daniel Galloway,Grace Chan,Kerry-Ann O’Grady,Chris Wadsworth,Panagiotis Vlavianos,Jonathan R. Potts,Shivan Sivakumar,Brian R Davidson,Marc G. Besselink,Rutger‐Jan Swijnenburg,Long R. Jiao,Geert Kazemier,Elisa Giovannetti,Jonathan Krell,Adam E. Frampton
标识
DOI:10.1097/js9.0000000000001888
摘要
Background: Biliary obstruction can be due to both malignant and benign pancreaticobiliary disease. Currently, there are no biomarkers that can accurately help make this distinction. MicroRNAs (miRNAs) are stable molecules in tissue and biofluids that are commonly deregulated in cancer. The MIRABILE study aimed to identify miRNAs in bile that can differentiate malignant from benign pancreaticobiliary disease. Materials and Methods: There were 111 patients recruited prospectively at endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) for obstructive jaundice, and bile was aspirated for cell-free RNA (cfRNA) extraction and analysis. In a discovery cohort of 78 patients (27 with pancreatic ductal adenocarcinoma (PDAC), 14 cholangiocarcinoma (CCA), 37 benign disease), cfRNA was subjected to small-RNA sequencing. LASSO regression was used to define bile miRNA signatures, and NormFinder to identify endogenous controls. In a second cohort of 87 patients (34 PDAC, 14 CCA, 39 benign disease), RT-qPCR was used for validation. Results: LASSO regression identified 14 differentially-expressed bile miRNAs of which 6 were selected for validation. When comparing malignant and benign pancreaticobiliary disease, bile miR-340 and miR-182 were validated and significantly differentially expressed ( P <0.05 and P <0.001, respectively). This generated an AUC of 0.79 (95%CI 0.70-0.88, sensitivity 65%; specificity 82%) in predicting malignant disease. Conclusion: Bile collected during biliary drainage contains miRNAs able to differentiate benign from malignant pancreaticobiliary diseases in patients with obstructive jaundice. These bile miRNAs have the potential to increase diagnostic accuracy.
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