MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study
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Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2024-10
Date Acceptance
2024-06-16
Citation
International Journal of Surgery, 2024, 110 (10), pp.6518-6527
ISSN
1743-9159
Publisher
Wolters Kluwer
Start Page
6518
End Page
6527
Journal / Book Title
International Journal of Surgery
Volume
110
Issue
10
Copyright Statement
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed
under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://journals.lww.com/international-journal-of-surgery/abstract/9900/micrornas_as_bile_based_biomarkers_in.1834.aspx
Publication Status
Published
Date Publish Online
2024-07-23