Expression of liver cancer stem cell markers and association with recurrence and survival in hepatocellular carcinoma

doi:10.4252/wjsc.v18.i5.119123

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World Journal of Stem Cells

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1948-0210

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

Retrospective Study

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 Stem Cells. May 26, 2026; 18(5): 119123
Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.119123

Expression of liver cancer stem cell markers and association with recurrence and survival in hepatocellular carcinoma

Xing-Qing Jia, Shuai Han, Yan-Sheng Shang, Fan-Guo Kong, Lin Qi, Cheng-Liang Wang, Wu-Jun Xiong

Xing-Qing Jia, Shuai Han, Yan-Sheng Shang, Fan-Guo Kong, Cheng-Liang Wang, Department of Gastroenterology, Jinan City People’s Hospital, Jinan 250000, Shandong Province, China

Xing-Qing Jia, Department of Gastroenterology, Shandong University, Jinan 250100, Shandong Province, China

Lin Qi, Department of Gastroenterology, Jinan Laiwu District People’s Hospital, Jinan 250022, Shandong Province, China

Wu-Jun Xiong, Department of Gastroenterology, Fudan University Affiliated Pudong Hospital, Shanghai 201399, China

Author contributions: Jia XQ conceived and designed the study, collected clinical data, performed immunohistochemical experiments, conducted statistical analyses, and drafted the manuscript; Han S and Shang YS participated in the data acquisition, pathological evaluation, and follow-up data collection; Kong FG and Qi L were responsible for patient enrollment, clinical data verification, and the interpretation of clinical variables; Wang CL contributed to the immunohistochemical staining procedures and quality control of pathological assessments; Xiong WJ supervised the entire study, critically revised the manuscript for important intellectual content, obtained funding support, and approved the final version for publication. All the authors have read and approved the final version of the manuscript.

AI contribution statement: We confirm that no artificial intelligence tools were used in writing this manuscript. No part of the Main Text of the manuscript (including Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion) was generated by AI. All content was written independently by the authors. No AI tools were used for language polishing, translation, data analysis, or any form of writing assistance. No AI tools were involved in the design of the study, data interpretation, or formulation of the results and conclusions. No images, figures, or graphical materials in this manuscript were generated by AI. All authors take full responsibility for the originality, integrity, and accuracy of the work.

Supported by Clinical Medicine Emerging Specialty (or Specific Disease) Program of the Pudong New Area Health Commission, No. 2025-PWXZ-05; and Science and Technology Development Fund of Shanghai Pudong New Area, No. PKJ2024-Y54.

Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Jinan People’s Hospital, No. 20240530009.

Informed consent statement: Owing to the retrospective nature of the study, the Ethics Committee waived the requirement for informed consent.

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

Data sharing statement: No additional data are available.

Corresponding author: Wu-Jun Xiong, MD, Chief Physician, Department of Gastroenterology, Fudan University Affiliated Pudong Hospital, No. 2800 Gongwei Road, Huinan Town, Pudong New Area, Shanghai 201399, China. xiongwujun25@163.com

Received: January 27, 2026
Revised: March 2, 2026
Accepted: April 7, 2026
Published online: May 26, 2026
Processing time: 117 Days and 23 Hours

Abstract

BACKGROUND

Postoperative recurrence and cancer-related mortality remain significant challenges following curative resection for hepatocellular carcinoma (HCC). Conventional clinicopathological parameters inadequately capture tumor biological heterogeneity; therefore, reliable tissue biomarkers that reflect stemness-associated aggressiveness are required for early postoperative risk stratification.

AIM

To evaluate liver cancer stem cell (CSC) markers (EpCAM, CD133, CK19, and CD44) in HCC and their prognostic value for recurrence and survival.

METHODS

A total of 132 patients with pathologically confirmed HCC who underwent radical resection at Jinan City People’s Hospital (January 2019 to December 2023) were retrospectively included. Tumor expression of EpCAM, CD133, CK19, and CD44 was assessed by immunohistochemistry using predefined thresholds. High CSC expression was defined as positivity for at least two markers. The primary outcomes were relapse-free survival and overall survival. Survival was analyzed using the Kaplan-Meier method and the log-rank test. Independent prognostic factors and risk scores were identified by Cox regression. Predictive performance for 3-year outcomes was assessed using receiver operating characteristic curves and the C-index.

RESULTS

A total of 45 cases (34.09%) were positive for EpCAM, 42 (31.82%) for CD133, 31 (23.48%) for CK19, and 62 (46.97%) for CD44. High expression was observed in 56 cases (42.42%) of CSC. The median follow-up time was 42 months. Relapse occurred in 66 cases (50.00%), and 43 patients (32.58%) died. The 3-year overall survival rate in CK19-positive patients was 51.61%, which was lower than 78.22% in CK19-negative patients (Log-rank χ² = 10.564, P = 0.001). Multivariate Cox regression analysis revealed that CK19 positivity and microvascular invasion were independent factors for poor prognosis. The area under the curve for 3-year mortality increased from 0.726 to 0.788, while the C-index rose from 0.684 to 0.725 after the addition of the CSC marker.

CONCLUSION

The CSC-associated markers in HCC (CK19 and CD133 in particular) are closely related to postoperative recurrence and survival, and their combined assessment enhances risk stratification.

Keywords: Hepatocellular carcinoma; Cancer stem cells; EpCAM; CD133; CK19; CD44; Recurrence; Prognosis

Core Tip: Postoperative recurrence is common after curative resection of hepatocellular carcinoma, highlighting the need for improved tissue-based risk stratification. We assessed four cancer stem cell-associated markers (EpCAM, CD133, CK19, and CD44) by immunohistochemistry in resected hepatocellular carcinoma. CK19 and CD133 were identified to carry prognostic information, and combined multi-marker assessment improved risk discrimination beyond routine clinicopathological factors. immunohistochemistry-based cancer stem cell profiling may help identify patients who require intensified surveillance and individualized postoperative management.