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 Gastroenterol. Sep 7, 2026; 32(33): 118587
Published online Sep 7, 2026. doi: 10.3748/wjg.118587
Published online Sep 7, 2026. doi: 10.3748/wjg.118587
Urinary cell-free DNA as a noninvasive liquid biopsy for hepatocellular carcinoma
Amy K Kim, James Hamilton, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Selena Y Lin, Surbhi Jain, Fwu-Shan Shieh, Dmitry Goryunov, Zhili Wang, JBS Science Inc., Doylestown, PA 18902, United States
Hsin-Ni Liu, Ying-Hsiu Su, Baruch S. Blumberg Institute, Doylestown, PA 18902, United States
Terence P Gade, Department of Radiology, University of Pennsylvania Hospital, Philadelphia, PA 19104, United States
Hie-Won Hann, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
Ting-Tsung Chang, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan
Author contributions: Kim AK obtained patient specimens; Lin SY devised the experimental plans, supervised execution, and analyzed the data; Liu HN edited the manuscript; Jain S conceived and executed the experiments; Wang Z developed the cell-free DNA isolation method; Gade TP, Hamilton J, Hann HW, and Chang TT obtained the patient specimens; Su YH conceived the study and coordinated the experimental plans; Kim AK and Su YH co-wrote the manuscript; Liu HN, Shieh FS, and Goryunov D performed data analysis; Liu HN and Shieh FS produced the figures.
AI contribution statement: No AI tools were used in the preparation, writing, editing, or revision of this manuscript.
Supported by the National Institutes of Health, W81XWH-20-1-0605 and 1K08CA237624-01A1 to Kim AK, 5R44HG008700-03 to Wang Z, 5R01CA202769-05 and 1U01CA275648-01 to Su YH, 5R44CA165312-07 and 1R43AI167169-01 to Lin SY.
Institutional review board statement: This study was approved by the Heartland Institutional Review Board. Specimen collections from participants were approved by each study center’s Institutional Review Board (Thomas Jefferson University, Johns Hopkins Medicine, National Cheng Kung University Hospital, and University of Pennsylvania). This study was conducted in accordance with both the Declarations of Helsinki and Istanbul. Written informed consent was received from all participants prior to enrollment.
Conflict-of-interest statement: Lin SY, Jain S, Wang Z, and Su YH are shareholders of JBS Science Inc. All other authors declare no competing interests.
Data sharing statement: The sequencing data are available at NCBI SRA under BioProject number PRJNA1365867. The data generated during the study are available from the corresponding author upon reasonable request.
Corresponding author: Ying-Hsiu Su, PhD, Chief, Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States. ying-hsiu.su@bblumberg.org
Received: January 13, 2026
Revised: March 10, 2026
Accepted: May 15, 2026
Published online: September 7, 2026
Processing time: 208 Days and 15.5 Hours
Revised: March 10, 2026
Accepted: May 15, 2026
Published online: September 7, 2026
Processing time: 208 Days and 15.5 Hours
Core Tip
Core Tip: Urinary cell-free DNA may serve as a simple, noninvasive tool for detecting liver cancer (hepatocellular carcinoma). In this study, we found that urine contains shorter, tumor-specific DNA fragments and unique genetic markers that help distinguish liver cancer patients from those with other chronic liver conditions. With similar accuracy to blood-based tests and the advantage of easier sample collection, urine cell-free DNA has the potential to improve liver cancer diagnosis and monitoring.