Wei YH, Jiang WJ, Wang SQ, Cai YL, Ma XL. Cancer-associated fibroblasts, clinicopathological characteristics and prognosis of liver cancer: A systematic review and meta-analysis based on real-world research. World J Gastrointest Oncol 2025; 17(12): 110395 [DOI: 10.4251/wjgo.v17.i12.110395]
Corresponding Author of This Article
Xue-Lei Ma, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. drmaxuelei@gmail.com
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Oncology
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Meta-Analysis
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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/
Dec 15, 2025 (publication date) through Dec 17, 2025
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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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Wei YH, Jiang WJ, Wang SQ, Cai YL, Ma XL. Cancer-associated fibroblasts, clinicopathological characteristics and prognosis of liver cancer: A systematic review and meta-analysis based on real-world research. World J Gastrointest Oncol 2025; 17(12): 110395 [DOI: 10.4251/wjgo.v17.i12.110395]
World J Gastrointest Oncol. Dec 15, 2025; 17(12): 110395 Published online Dec 15, 2025. doi: 10.4251/wjgo.v17.i12.110395
Cancer-associated fibroblasts, clinicopathological characteristics and prognosis of liver cancer: A systematic review and meta-analysis based on real-world research
Yu-Hao Wei, Wen-Jing Jiang, Shi-Qian Wang, Yu-Long Cai, Xue-Lei Ma
Yu-Hao Wei, Xue-Lei Ma, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Wen-Jing Jiang, Shi-Qian Wang, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Yu-Long Cai, Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Yu-Long Cai, Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Co-corresponding authors: Yu-Long Cai and Xue-Lei Ma.
Author contributions: Wei YH was responsible for conceptualization, methodology, literature retrieval, data curation, original draft writing, and revision; Jiang WJ and Wang SQ each participated in literature retrieval, data curation, and revision; Cai YL provided expert guidance during the major revision, contributed to conceptual refinement, and critically reviewed the revised manuscript; Ma XL took charge of supervision, critical revision of the manuscript, and project administration; and project administration; Cai YL and Ma XL contributed equally to this article, they are the co-corresponding authors of this manuscript; and all the authors have read and agreed to the final version of the manuscript.
Supported by the Sichuan Science and Technology Program, No. 2024NSFSC1936.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Xue-Lei Ma, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. drmaxuelei@gmail.com
Received: June 10, 2025 Revised: July 22, 2025 Accepted: October 23, 2025 Published online: December 15, 2025 Processing time: 188 Days and 2.3 Hours
Abstract
BACKGROUND
Cancer-associated fibroblasts (CAFs), crucial components of the tumor microenvironment in primary and metastatic tumors, can impact the activity of cancer cells and contribute to their progression. Given their extensive interactions with cancer cells and other stromal cells, we aimed to evaluate the prognostic value of CAFs in patients with liver cancer (LC).
AIM
To investigate the association between CAF expression and clinicopathological characteristics as well as overall survival (OS) in patients with LC, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA).
METHODS
We performed a meta-analysis of cohort studies with available data on the effects of CAF expression on both clinicopathological characteristics and OS via hazard ratios (HRs) and risk ratios with 95% confidence intervals (CIs). Studies were subgrouped on the basis of CAF markers and cancer type, and the subgroup effects of CAF expression on both HCC and iCCA were analyzed through meta-regression. The Newcastle-Ottawa Scale was used to evaluate the included studies to guarantee their quality and minimize the possibility of bias.
RESULTS
Nine trials were selected and included a total of 1518 patients. According to our primary meta-analysis, the expression of CAFs in LC patients was significantly associated with a decrease in OS (LC: HR: 1.62; 95%CI: 1.34-1.97; P < 0.001; HCC: HR: 1.67; 95%CI: 1.34-2.07; P < 0.001; iCCA: HR: 1.47; 95%CI: 0.97-2.23; P = 0.07); nevertheless, it was not significantly associated with almost all clinicopathologic characteristics, including tumor size, venous infiltration, alpha-fetoprotein level, and differentiation grade. According to the subgroup analysis of smooth muscle actin (SMA) markers in both HCC patients and iCCA patients, high CAF expression in HCC (HR: 2.29; 95%CI: 1.01-5.22; P = 0.048) and iCCA (HR: 2.04; 95%CI: 1.09-3.81; P = 0.025) patients was a significant indicator of poor OS. Moreover, the clinicopathological characteristics were also verified by the SMA marker, which had a nearly significant effect on the venous infiltration of iCCA (risk ratio: 2.70; 95%CI: 0.97-7.49; P = 0.057).
CONCLUSION
High CAF expression, evaluated by both mixed markers and SMAs, is significantly associated with poor OS in patients with LC, including both HCC patients and iCCA patients. However, further research is necessary since how CAF expression and clinicopathologic features are related is yet unknown.
Core Tip: This meta-analysis reveals that high expression of cancer-associated fibroblasts (CAFs), particularly marked by α-smooth muscle actin, is significantly associated with poor overall survival in liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. CAFs serve as a robust prognostic biomarker, with stronger predictive value in hepatocellular carcinoma. While their impact on clinicopathological features remains inconclusive, these findings highlight CAFs as potential therapeutic targets. Further research is needed to clarify their role in tumor progression and optimize clinical applications.
