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World J Gastroenterol. Jan 21, 2026; 32(3): 113187
Published online Jan 21, 2026. doi: 10.3748/wjg.v32.i3.113187
Stemness CD24 activation promotes hepatocellular carcinoma progression via an immune escape mechanism
Yin Cai, Lu-Yin Liu, Xiao-Xiao Xia, Hao Tang, Min Xu, Wen-Li Sai, Deng-Fu Yao, Min Yao
Yin Cai, Department of Oncology, Xinghua People’s Hospital, Xinghua 225700, Jiangsu Province, China
Lu-Yin Liu, Department of Immunology, Nantong University, Nantong 226001, Jiangsu Province, China
Xiao-Xiao Xia, Department of Infectious Diseases, Haian People’s Hospital, Haian 226600, Jiangsu Province, China
Hao Tang, Min Yao, Department of Immunology, Medical School of Nantong University, Nantong University, Nantong 226001, Jiangsu Province, China
Min Xu, Wen-Li Sai, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Co-first authors: Yin Cai and Lu-Yin Liu.
Co-corresponding authors: Deng-Fu Yao and Min Yao.
Author contributions: Cai Y, Liu LY, Xia XX and Tang H conceptualized and designed the research; Cai Y and Xia XX screened patients and acquired clinical data; Liu LY, Tang H and Sai WL collected blood samples and performed laboratory analysis; Yao M, Sai WL and Xia XX acquired the funding and wrote the manuscript. Yao M and Yao DF conceptualized, designed, and supervised and submitted the study. All the authors have read and approved the final manuscript. Cai Y proposed, designed and conducted stemness CD24 analysis, performed data analysis and prepared the first draft of the manuscript. Liu LY was responsible for patient screening, enrollment, collection of clinical data and blood specimens. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Yao M and Yao DF have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Yao M applied for and obtained the funds for this research project. Yao DF conceptualized, designed, and supervised the whole process of the project. He searched the literature, revised and submitted the early version of the manuscript with the focus on the association between CD24 and hepatocytes. Yao M was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript with a new focus on CD24 as the predictors of HCC and on potential underlying mechanisms. This collaboration between Yao M and Yao DF is crucial for the publication of this manuscript and other manuscripts still in preparation.
Supported by National Natural Science Foundation of China, No. 32470985; Nantong S & T Programs of China, No. MS2024051; and Federation for Prevention & Control of Infectious Diseases of China, No. NTCRB2025016.
Institutional review board statement: Patient recruitment was approved by the Ethics Committee of Nantong University (No. 2018-L026).
Institutional animal care and use committee statement: The study involving the rat model was approved by the guidelines of the Animal Care and Use Committee of Nantong University (No. S20200318-017).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
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: Min Yao, PhD, Postdoc, Professor, Department of Immunology, Medical School of Nantong University, Nantong University, No. 19 Qixiu Road, Nantong 226001, Jiangsu Province, China. erbei@ntu.edu.cn
Received: August 19, 2025
Revised: September 10, 2025
Accepted: November 26, 2025
Published online: January 21, 2026
Processing time: 151 Days and 11 Hours
Abstract
BACKGROUND

Cluster of differentiation 24 (CD24) serves as a liver cancer stem cell marker, and its upregulation is related to chronic liver disease malignancy. However, the exact relationship between CD24 expression and hepatocarcinogenesis remains unknown.

AIM

To investigate CD24 levels among individuals with chronic liver diseases and confirm the alterations in CD24 and programmed death-ligand 1 (PD-L1) expression in a dynamic model of rat hepatocarcinogenesis.

METHODS

Approved by the ethics committee, CD24 levels were detected in the serum of 129 patients with hepatocellular carcinoma (HCC), 72 patients with chronic hepatitis (CH), 60 patients with liver cirrhosis (LC) and 111 normal control (NC). Receiver operating characteristic curves and clinicopathological characteristics of CD24 were used to evaluate the diagnostic or prognostic value for HCC, and the CD24+ T lymphocyte ratio and dynamic alterations in CD24 and PD-L1 expression were confirmed in a rat HCC model.

RESULTS

Compared with those in the CH, LC and NC groups, the average CD24 level in the HCC group was significantly greater (P < 0.01). The CD24+ T-cell ratio in the HCC group was greater than that in the CH or NC group. Clinicopathological characteristics of high CD24 in HCC patients included hepatitis B virus infection, single/multicenter status, tumor size, lymph node or extrahepatic metastasis, differentiation degree, tumor-node-metastasis grade, Child-Pugh score, portal vein tumor thrombus and poor prognosis. Mechanistically, CD24 is dynamically upregulated during hepatocarcinogenesis and closely positively correlated with PD-L1 for immune escape, metastasis (CD44), and with respect to HCC markers (Wnt3a, GPC-3 and alpha-fetoprotein).

CONCLUSION

Activated CD24 promoted HCC formation through programmed death-ligand 1 signaling and could be a valuable biomarker for monitoring chronic liver disease malignancy.

Keywords: Clusters of differentiation 24; Hepatocarcinogenesis; Programmed death-ligand 1; Biomarker; Chronic liver disease

Core Tip: Upregulated clusters of differentiation 24 (CD24) expression is associated with hepatocellular carcinoma progression. CD24, a marker of liver cancer stem cells, might exert its oncogenic regulatory effects on the malignancy of chronic liver diseases through the activation of programmed death-ligand 1 signaling. Clinical investigations and hepatocarcinogenesis models have confirmed that upregulated CD24 promotes hepatocyte malignancy via immune escape mechanisms and could be a favorable biomarker for monitoring hepatocarcinogenesis.