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Published on: June 13, 2016
MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study
Daniel S K Liu1, Jisce R Puik2,3, Morten T Venø4,5
1Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
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.
Insights
Bile microRNAs (miRNAs) can distinguish malignant from benign pancreaticobiliary disease. This finding may improve diagnostic accuracy for obstructive jaundice using biomarkers in bile.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Biliary obstruction presents diagnostic challenges, lacking specific biomarkers to differentiate malignant from benign causes.
- MicroRNAs (miRNAs) are stable RNA molecules found in biofluids and tissues, often dysregulated in cancers.
- The MIRABILE study investigated bile miRNAs as potential diagnostic markers for pancreaticobiliary diseases.
Purpose of the Study:
- To identify specific microRNA (miRNA) signatures in bile capable of differentiating malignant from benign pancreaticobiliary diseases.
- To evaluate the diagnostic potential of bile miRNAs in patients with obstructive jaundice.
Main Methods:
- Prospective recruitment of 111 patients undergoing ERCP or PTC for obstructive jaundice.
- Bile aspiration for cell-free RNA (cfRNA) extraction and small-RNA sequencing in a discovery cohort (n=78).
- LASSO regression for miRNA signature identification and RT-qPCR validation in a second cohort (n=87).
Main Results:
- LASSO regression identified 14 differentially expressed bile miRNAs; 6 were selected for validation.
- Bile miR-340 and miR-182 were significantly differentially expressed between malignant and benign groups (P <0.05 and P <0.001).
- A diagnostic model using these miRNAs achieved an AUC of 0.79 (95% CI: 0.70-0.88), with 65% sensitivity and 82% specificity for malignant disease.
Conclusions:
- Bile collected during biliary drainage harbors miRNAs that can differentiate benign from malignant pancreaticobiliary conditions.
- These identified bile miRNAs demonstrate potential for enhancing diagnostic accuracy in obstructive jaundice.
- Further research into bile miRNA profiles could lead to novel non-invasive diagnostic tools for pancreaticobiliary diseases.
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