# Exploring microRNAs in Bile Duct Stents as Diagnostic Biomarkers for Biliary Pathologies

## TL;DR

This study explores whether microRNAs from bile duct stents can serve as biomarkers to diagnose biliary diseases, including cancer.

## Contribution

The study demonstrates that microRNAs can be reliably extracted from bile duct stents and may reflect disease states.

## Key findings

- MicroRNAs miR-16, miR-21, and miR-223 were reliably detected in bile duct stent samples.
- Significant increases in miR-16, miR-21, and miR-223 were found in patients with cholangitis compared to non-inflammatory cases.
- No significant differences in miRNA levels were observed between malignant and non-malignant groups.

## Abstract

The optimal diagnosis of malignant diseases of the bile duct remains a challenge and can affect management and, subsequently, outcomes. Obstructive cholestasis is one of the most common manifestations of both benign and malignant disease and is commonly treated with stent placement. In this proof-of-principle study, we investigated whether specimens from bile duct stents could serve as a source of biomarkers for changes in patients with bile duct disease, including inflammation and malignancy. The data showed that microRNAs can be reliably detected in samples and that the subset of microRNAs may reflect disease states, supporting further screening for the most appropriate targets to diagnose malignant biliary disease.

Background/Objectives: Obstruction of the biliary duct may be caused by various conditions ranging from chronic inflammation to neoplasia, including cholangiocarcinoma (CCA). While the definite histological diagnosis of intrahepatic lesions is relatively straightforward, the diagnostic workup of biliary duct stenosis can be challenging, despite the availability of novel tools for intraductal diagnosis. This proof-of-principle study aimed to investigate whether microRNAs (miRNAs) from bile duct stents may be used as biomarkers to differentiate between various bile duct diseases. Methods: For this purpose, we included 100 patients with one or more bile duct stents for various reasons, including malignant disease (n = 40), stenosis due to liver transplantation or surgery (n = 60), and cholangitis (n = 42). During endoscopic retrograde cholangiography, the stents were collected, and miRNA analyses were performed to evaluate miR-16, miR-21, and miR-223. Results: All studied miRNAs were successfully detected from the specimens obtained from the bile duct stents and were comparable in different stents from the same subjects. Following normalization, significant increases in miR-16, -21, and -223 levels were identified in patients with cholangitis compared to specimens from a non-inflammatory cohort. However, when comparing the data from patients in the malignant and non-malignant cohorts, the individual levels of miR-16, miR-21, and miR-223 showed high variation, without reaching a statistically significant difference. Conclusions: In summary, bile duct stents can be considered as potential sources of intraductal biomarkers, specifically miRNAs. Further profiling and validation analyses are necessary to identify the most appropriate miRNA targets for differentiating bile duct diseases.