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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
MicroRNA-126-3p as a predictive biomarker for patients with primary biliary cholangitis refractory to ursodeoxycholic acid
Shi-Da Pan, Chu-Yue Xiong, Ying-Juan Shen, Jia-He Tian, Yi-Lin Wang, Jia-Ning Wang, Si-Yu Wang, Feng-Yi Li, Li-Feng Wang, Qin Qiu, Luo Yang, Xiao-Meng Liu, Jun-Qing Luan, Zheng-Sheng Zou, Fu-Sheng Wang, Fan-Ping Meng
Shi-Da Pan, Chu-Yue Xiong, Ying-Juan Shen, Jia-He Tian, Yi-Lin Wang, Jia-Ning Wang, Si-Yu Wang, Feng-Yi Li, Li-Feng Wang, Qin Qiu, Luo Yang, Xiao-Meng Liu, Jun-Qing Luan, Fu-Sheng Wang, Fan-Ping Meng, Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
Shi-Da Pan, Beijing Ditan Hospital, Capital Medical University, Beijing 100069, China
Chu-Yue Xiong, Jia-He Tian, Jia-Ning Wang, 302 Clinical Medical School, Peking University, Beijing 100039, China
Zheng-Sheng Zou, Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
Co-first authors: Shi-Da Pan and Chu-Yue Xiong.
Co-corresponding authors: Fu-Sheng Wang and Fan-Ping Meng.
Author contributions: Wang FS and Meng FP designed the study, they contributed equally to this manuscript and are co-corresponding authors. Pan SD and Xiong CY analyzed the data and drafted the paper, they contributed equally to this manuscript and are co-first authors. Shen YJ, Tian JH, Wang YL, Wang JN, Wang SY, Li FY, Wang LF, Yang L, and Liu XM collected the data; Shen YJ, and Zou ZS revised the manuscript; Qiu Q and Luan JQ reviewed the data. All authors have approved the final version of the manuscript.
Supported by the National Key Research and Development Program of China, No. 2019YFC0840704; and Beijing Municipal Science and Technology Program, No. Z201100005520047.
Institutional review board statement: This study was reviewed and approved by the Medical Ethics Committee of the 302 Clinical Medical School (Approval No. 2016174D).
Informed consent statement: Informed consent was obtained from each patient included in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Restrictions apply to the availability of these data and so they are not publicly available. However, data are available from the corresponding author upon reasonable request and with the permission of the institution.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Fan-Ping Meng, MD, PhD, Associate Professor, Chief Physician, Postdoc, Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, No. 100 West Fourth Ring Middle Road, Fengtai District, Beijing 100039, China.
drmengfanping@126.com
Received: May 26, 2025
Revised: June 21, 2025
Accepted: July 31, 2025
Published online: August 21, 2025
Processing time: 86 Days and 20.3 Hours
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 (n = 10) and validation group (n = 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 (N = 40). MiR-22-5p and miR-126-3p were highly expressed in the DS group before treatment (P < 0.001), whereas miR-7706 exhibited a low expression (P = 0.017). Post-treatment, miR-126-3p maintained low expression in the drug-resistant group (P = 0.003), but showed elevated levels in the DS group (P < 0.001). Logistic regression analysis identified miR-126-3p expression (odds ratio = 34.32, 95% confidence interval: 1.95-605.40, P = 0.016) as a significant factor influencing UDCA treatment response, while miR-22-5p (P = 0.990) and miR-7706 (P = 0.157) showed no significant association. MiR-126-3p levels were negatively correlated with total bilirubin (r = -0.356, P = 0.005) and immunoglobulin G levels (r = -0.311, P = 0.015). The area under the receiver operating characteristic curve was 0.891 (P = 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.
Core Tip: Patients with primary biliary cholangitis exhibit variable responses to ursodeoxycholic acid (UDCA) therapy, and reliable predictive biomarkers before therapy remain elusive. This study identified 49 differentially expressed microRNAs in patients with different response and explore their potential as predictive biomarkers. MiR-126-3p maintained low expression in the drug-resistant group while showing elevated levels in the sensitive group after therapy. Its expression was significantly positively correlated with UDCA efficacy and negatively associated with total bilirubin and immunoglobulin G levels. The receiver operating characteristic curve analysis demonstrated an area under the curve of 0.891 with a sensitivity of 82.4% and specificity of 84.6%, demonstrating high predictive potential value in patient’s refractory to UDCA.
