Integrated diagnostic model based on serum exosomal microRNAs and functional mechanism of miR-200b-3p in hepatocellular carcinoma

doi:10.4251/wjgo.118948

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Sep 15, 2026; 18(9): 118948
Published online Sep 15, 2026. doi: 10.4251/wjgo.118948

Integrated diagnostic model based on serum exosomal microRNAs and functional mechanism of miR-200b-3p in hepatocellular carcinoma

Xiao-Ye Sun, Na Fu, Dan-Dan Zhao, Zheng-Lu Wang, Lei Cao, Jia-Li Qiu, Yi Li, Wei Gao, Jin-Liang Duan, Lin Li, Yue-Min Nan

Xiao-Ye Sun, Na Fu, Dan-Dan Zhao, Yue-Min Nan, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital, Shijiazhuang 050051, Hebei Province, China

Xiao-Ye Sun, Na Fu, Dan-Dan Zhao, Yue-Min Nan, Department of Gastroenterology, Hebei Medical University Third Hospital, Shijiazhuang 050051, Hebei Province, China

Xiao-Ye Sun, Na Fu, Dan-Dan Zhao, Yue-Min Nan, Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, Shijiazhuang 050051, Hebei Province, China

Xiao-Ye Sun, Na Fu, Dan-Dan Zhao, Yue-Min Nan, Hebei Provincial Key Laboratory of Liver Fibrosis Mechanism Study in Chronic Liver Diseases, Hebei Medical University Third Hospital, Shijiazhuang 050051, Hebei Province, China

Zheng-Lu Wang, Lei Cao, Jia-Li Qiu, Yi Li, Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin 300380, China

Wei Gao, Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300380, China

Jin-Liang Duan, School of Medicine, Nankai University, Tianjin 300071, China

Lin Li, Institute of Transplantation, Tianjin First Central Hospital, Tianjin 300380, China

Author contributions: Sun XY and Fu N contributed to methodology; Sun XY, Qiu JL, Li Y, and Zhao DD contributed to investigation; Sun XY contributed to data curation and writing the original draft; Wang ZL and Cao L contributed to supervision; Qiu JL and Li Y contributed to visualization; Gao W contributed to resources; Duan JL contributed to validation; Li L contributed to formal analysis; Nan YM contributed to conceptualization, funding acquisition and writing - review and editing. All authors approved the final version of the article.

AI contribution statement: AI tools (specifically DeepSeek and Grammarly) were used to assist with manuscript writing and language polishing. The core content and scientific ideas were originally written by the authors. AI tools provided assistance only in portions of the writing process (e.g., language refinement and sentence structuring). All AI-generated or AI-suggested content was subsequently reviewed and revised by the authors, who take full responsibility for the final manuscript.

Supported by Key Research and Development Program of Hebei Province-Biomedical Innovation Project, No. 23377705D; and Introduction of Foreign Intelligence Program in Hebei Province in 2024.

Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Hebei Medical University Third Hospital, No. KS2023-071-1.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The datasets, technical appendix, and statistical code used in this study are available from the corresponding author upon reasonable request. Participants gave informed consent for data sharing, and all shared data will be anonymized. No additional data are available.

Corresponding author: Yue-Min Nan, MD, PhD, Chief, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang 050051, Hebei Province, China. nanyuemin@hebmu.edu.cn

Received: January 15, 2026
Revised: March 20, 2026
Accepted: May 14, 2026
Published online: September 15, 2026
Processing time: 222 Days and 22.7 Hours

Abstract

BACKGROUND

The early detection of hepatocellular carcinoma (HCC) remains a major clinical challenge due to the limited sensitivity and specificity of current biomarkers. This study sought to develop a diagnostic model based on serum exosomal microRNAs (miRNAs) and to elucidate the functional mechanism of a key miRNA, miR-200b-3p, in HCC pathogenesis.

AIM

To develop and validate a serum exosomal miRNA-based diagnostic model for HCC.

METHODS

Serum exosomes were isolated from a discovery cohort (68 HCC, 131 non-HCC) and a validation cohort (66 HCC, 135 non-HCC). Candidate miRNAs were identified via next-generation sequencing and machine learning, and validated by quantitative real-time polymerase chain reaction. A diagnostic model was constructed using logistic regression. The role of miR-200b-3p was examined using in vitro functional assays.

RESULTS

A diagnostic model incorporating three exosomal miRNAs (miR-200b-3p, miR-215-5p, miR-452-5p) and age was established. It showed strong performance in the training set (area under the curve = 0.863, sensitivity = 86.4%, specificity = 76.5%; all P < 0.001). Mechanistically, miR-200b-3p acted as a tumor suppressor by directly targeting phosphoserine aminotransferase 1. Its overexpression inhibited HCC cell proliferation, migration, and invasion (all P < 0.05), while knockdown promoted these phenotypes (all P < 0.05).

CONCLUSION

This study establishes and validates a non-invasive exosomal miRNA-based diagnostic model for HCC, reveals that miR-200b-3p directly targets phosphoserine aminotransferase 1, and provides mechanistic support for early detection.

Keywords: Hepatocellular carcinoma; Exosomal microRNAs; Diagnostic model; MicroRNA-200b-3p; Phosphoserine aminotransferase 1; Liquid biopsy

Core Tip: This study developed and validated a novel three-exosomal-miRNA (miR-200b-3p, miR-215-5p, miR-452-5p) and age-based diagnostic model for hepatocellular carcinoma (HCC) using a rigorous multi-cohort design. The model demonstrated high accuracy with an area under the curve of 0.863, offering a robust non-invasive tool for early detection. Furthermore, we experimentally identified phosphoserine aminotransferase 1 as a direct functional target of miR-200b-3p, establishing its tumor-suppressive role in HCC. Our work provides both a clinically promising liquid biopsy biomarker panel and a key mechanistic insight, advancing the field of precision diagnosis for HCC.