Lulic I, Lulic D, Pavicic Saric J, Bacak Kocman I, Rogic D. Personalized translational medicine: Investigating YKL-40 as early biomarker for clinical risk stratification in hepatocellular carcinoma recurrence post-liver transplantation. World J Transplant 2025; 15(2): 103036 [DOI: 10.5500/wjt.v15.i2.103036]
Corresponding Author of This Article
Ileana Lulic, MD, Postdoctoral Fellow, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, Zagreb 10000, Croatia. ileanalulic@gmail.com
Research Domain of This Article
Transplantation
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Transplant. Jun 18, 2025; 15(2): 103036 Published online Jun 18, 2025. doi: 10.5500/wjt.v15.i2.103036
Personalized translational medicine: Investigating YKL-40 as early biomarker for clinical risk stratification in hepatocellular carcinoma recurrence post-liver transplantation
Ileana Lulic, Dinka Lulic, Jadranka Pavicic Saric, Iva Bacak Kocman, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zagreb 10000, Croatia
Dinka Lulic, Immediate Medical Care Unit, Saint James Hospital, Sliema SLM-1030, Malta
Dunja Rogic, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb 10000, Croatia
Dunja Rogic, Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, Zagreb 10000, Croatia
Author contributions: Lulic I, Lulic D, and Rogic D participated in the conceptualization of this manuscript; Lulic I, Lulic D, Pavicic Saric J, Bacak Kocman I, and Rogic D performed the literature review and data analysis; Lulic I, Lulic D, and Bacak Kocman I designed the manuscript's original draft; Pavicic Saric J, and Rogic D reviewed and edited the manuscript original draft; Lulic I, Lulic D, and Rogic D performed manuscript supervision and project administration; all of the authors approved the final version of the manuscript to be published.
Conflict-of-interest statement: There are no conflicts of interest to this manuscript.
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: Ileana Lulic, MD, Postdoctoral Fellow, Department of Anesthesiology, Intensive Care and Pain Medicine, Clinical Hospital Merkur, Zajceva 19, Zagreb 10000, Croatia. ileanalulic@gmail.com
Received: November 6, 2024 Revised: January 5, 2025 Accepted: January 14, 2025 Published online: June 18, 2025 Processing time: 107 Days and 16.9 Hours
Abstract
Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) presents a significant challenge, with recurrence rates ranging from 8% to 20% globally. Current biomarkers, such as alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), lack specificity, limiting their utility in risk stratification. YKL-40, a glycoprotein involved in extracellular matrix remodeling, hepatic stellate cell activation, and immune modulation, has emerged as a promising biomarker for post-LT surveillance. Elevated serum levels of YKL-40 are associated with advanced liver disease, tumor progression, and poorer post-LT outcomes, highlighting its potential to address gaps in early detection and personalized management of HCC recurrence. This manuscript synthesizes clinical and mechanistic evidence to evaluate YKL-40’s predictive utility in post-LT care. While preliminary findings demonstrate its specificity for liver-related pathologies, challenges remain, including assay standardization, lack of prospective validation, and the need to distinguish between malignant and non-malignant causes of elevated levels. Integrating YKL-40 into multi-biomarker panels with AFP and DCP could enhance predictive accuracy and enable tailored therapeutic strategies. Future research should focus on multicenter studies to validate YKL-40’s clinical utility, address confounding factors like graft rejection and systemic inflammation, and explore its role in predictive models driven by emerging technologies such as artificial intelligence. YKL-40 holds transformative potential in reshaping post-LT care through precision medicine, providing a pathway for better outcomes and improved management of high-risk LT recipients.
Core Tip: YKL-40 aligns with the principles of personalized translational medicine by offering a biomarker-driven approach to patient care. Its ability to provide liver-specific insights enables tailored post-liver transplantation surveillance and risk stratification, addressing the unique recurrence risks of individual patients. By integrating YKL-40 into multi-biomarker panels and predictive models, clinicians can refine therapeutic strategies, monitor disease progression more effectively, and personalize interventions for high-risk individuals. This targeted approach not only enhances clinical outcomes but also supports the broader shift toward precision medicine in transplantation, ensuring that care is both patient-specific and evidence-driven.
