MicroRNA-126-3p as a predictive biomarker for patients with primary biliary cholangitis refractory to ursodeoxycholic acid.

Background: Ursodeoxycholic acid (UDCA) is the first-line therapeutic agent for primary biliary cholangitis (PBC). However, a subset of patients exhibit a suboptimal response to UDCA, and reliable predictive biomarkers remain elusive. Studies have implicated plasma microRNAs (miRNAs) in the pathophysiological progression of PBC, with certain miRNAs demonstrating potential as diagnostic and disease progression biomarkers. However, biomarkers capable of predicting the therapeutic efficacy of UDCA have not yet been identified.

Aim: To investigate differentially expressed miRNAs in PBC patients with divergent UDCA treatment responses and to explore potential biomarkers that predict treatment response in PBC.

Methods: Plasma samples from treatment-naive PBC patients receiving ≥ 1 year of standard UDCA treatment were collected. Efficacy was evaluated using the Paris I criteria. Patient samples were divided into discovery group ( = 10) and validation group ( = 30), with further stratification of patients into drug-resistant and drug-sensitive (DS) cohorts. Next-generation sequencing and quantitative real-time polymerase chain reaction were used to screen, functionally analyze, and validate the pre-treatment miRNA profiles of the treatment groups.

Results: Forty-nine miRNAs were differentially expressed between the two groups before UDCA treatment ( = 40). MiR-22-5p and miR-126-3p were highly expressed in the DS group before treatment ( < 0.001), whereas miR-7706 exhibited a low expression ( = 0.017). Post-treatment, miR-126-3p maintained low expression in the drug-resistant group ( = 0.003), but showed elevated levels in the DS group ( < 0.001). Logistic regression analysis identified miR-126-3p expression (odds ratio = 34.32, 95% confidence interval: 1.95-605.40, = 0.016) as a significant factor influencing UDCA treatment response, while miR-22-5p ( = 0.990) and miR-7706 ( = 0.157) showed no significant association. MiR-126-3p levels were negatively correlated with total bilirubin ( = -0.356, = 0.005) and immunoglobulin G levels ( = -0.311, = 0.015). The area under the receiver operating characteristic curve was 0.891 ( = 0.0003, 95% confidence interval: 0.772-1.000) with a sensitivity of 82.4% and a specificity of 84.6%.

Conclusion: Plasma miRNA expression profiles are heterogenous in patients with PBC with differential responses to UDCA therapy. MiR-126-3p demonstrates predictive potential for a suboptimal response to UDCA in patients with PBC.