Endoscopic liquid biopsy of bile: superior diagnostic and prognostic performance of bile-derived exosomal miR-21-5p for biliary tract cancers.

Background: Compared to peripheral blood, bile as a microenvironment within the biliary tract is expected to contain a higher concentration of tumor-associated factors secreted directly by primary biliary tumors, making it a promising source for tumor analysis. This study explores the diagnostic and prognostic utility of exosomal miR-21-5p in bile and serum for biliary tract cancers (BTCs).

Methods: miR-21-5p expression was analyzed in 110 bile samples (55 BTC, 55 controls) collected during endoscopic retrograde cholangiopancreatography using qRT-PCR. The diagnostic and prognostic performances of miR-21-5p levels in bile and serum were evaluated. To enhance clinical applicability, we also developed a novel diagnostic parameter termed "miR-21-5p bile/serum (B/S) ratio", calculated by determining the ratio of bile to serum miR-21-5p within individuals.

Results: miR-21-5p expression was significantly elevated in both the bile and serum of patients with BTC. Bile miR-21-5p showed superior diagnostic performance (AUC: 0.913) over serum miR-21-5p (AUC: 0.628) and CA19-9 (AUC: 0.793). Prognostically, a higher bile miR-21-5p was associated with poorer overall survival and was identified as an independent predictor (HR: 2.446, p = 0.002), whereas serum miR-21-5p lacked significant prognostic value. B/S ratio also showed high diagnostic accuracy when ≥ 2 (AUC: 0.870), and a B/S ratio ≥ 13 was associated with significantly poorer overall survival and found as an independent prognostic predictor (HR: 2.554, p = 0.008).

Conclusions: Bile miR-21-5p and miR-21-5p B/S ratio are promising biomarkers for BTC diagnosis and prognosis that outperform traditional markers, highlighting the potential of bile-derived miRNAs for clinical use.