The diagnostic value of exosomal miRNAs in human bile of malignant biliary obstructions

Abstract

Background: Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease.

Aim: To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions.

Methods: Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction.

Results: In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74.

Conclusion: The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions.

Clinical trial registration no: NCT03102268.

Keywords: Biliary obstruction; Exosomes; MicroRNA; RNA se-quencing.