Xu ZF, Yao YR, Ye SY, Zhao CF. Citrullinated matrisome: An emerging stromal determinant in hepatocellular carcinoma prognostication. World J Gastrointest Oncol 2026; 18(9): 117335 [DOI: 10.4251/wjgo.117335]
Corresponding Author of This Article
Cheng-Fei Zhao, MD, PhD, Associate Professor, School of Pharmacy and Medical Technology, Putian University, No. 1133 Xueyuan Road, Chengxiang District, Putian 351100, Fujian Province, China. zhaochengfei209@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
editorial
Open-Access Policy of This Article
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World J Gastrointest Oncol. Sep 15, 2026; 18(9): 117335 Published online Sep 15, 2026. doi: 10.4251/wjgo.117335
Citrullinated matrisome: An emerging stromal determinant in hepatocellular carcinoma prognostication
Zhi-Feng Xu, Yu-Ru Yao, Shen-Yi Ye, Cheng-Fei Zhao
Zhi-Feng Xu, Department of Cardiothoracic Surgery, The 95th Hospital of Putian, Putian 351100, Fujian Province, China
Yu-Ru Yao, Shen-Yi Ye, Cheng-Fei Zhao, School of Pharmacy and Medical Technology, Putian University, Putian 351100, Fujian Province, China
Cheng-Fei Zhao, Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine, Putian University, Putian 351100, Fujian Province, China
Co-first authors: Zhi-Feng Xu and Yu-Ru Yao.
Author contributions: Xu ZF and Yao YR mainly wrote this paper and they contribute equally to this study as co-first authors; Zhao CF and Xu ZF mainly designed this paper; Xu ZF, Yao YR, Ye SY, and Zhao CF checked and proofread this paper; Xu ZF, Yao YR, Ye SY, and Zhao CF searched related literatures and information for this paper; all authors have read and approve the final manuscript.
AI contribution statement: The DeepSeek was used for language polishing, grammar correction, and minor phrasing improvements. The entire main text was written by the human authors. The AI tool (DeepSeek) was used only to refine sentence structure and correct grammatical errors. No portion of the scientific content, including original perspectives, critical evaluations, literature synthesis, or conclusions, was generated by AI. All critical interpretation and evaluation of the target article were performed solely by the human authors. Figure 1 was designed by the authors using standard vector graphics software (based on the conceptual framework described in the text). No AI image generation tools (e.g., DALL-E, Midjourney) were used.
Supported by Scientific Research Project of Putian University, No. 2022059; Special Project for Outstanding Young Talents of Putian University, No. 2024072; and Natural Science Foundation of Fujian Province, No. 2023J01160.
Conflict-of-interest statement: The authors declare that there is no conflict of interest in this paper.
Corresponding author: Cheng-Fei Zhao, MD, PhD, Associate Professor, School of Pharmacy and Medical Technology, Putian University, No. 1133 Xueyuan Road, Chengxiang District, Putian 351100, Fujian Province, China. zhaochengfei209@163.com
Received: December 5, 2025 Revised: December 21, 2025 Accepted: January 6, 2026 Published online: September 15, 2026 Processing time: 264 Days and 2.5 Hours
Abstract
Accurate prognostic stratification of hepatocellular carcinoma (HCC) remains a significant clinical challenge. Although the TNM staging system and serum alpha-fetoprotein levels provide a foundational framework for risk assessment, there is an urgent need for biomarkers that reflect the intrinsic biological aggressiveness of both the tumor and its microenvironment. In this editorial, we discuss the pivotal study published in the World Journal of Gastrointestinal Oncology by Cho et al, which identifies elevated expression of citrullinated glial fibrillary acidic protein (cit-GFAP) as a novel and independent prognostic marker associated with reduced overall survival (OS) following curative hepatic resection. We situate these findings within the broader context of HCC biology, highlighting the critical contributions of the tumor microenvironment and post-translational modifications. The study successfully bridges stromal biology with protein citrullination, demonstrating that high cit-GFAP expression is significantly correlated with increased mortality, independent of conventional prognostic factors such as tumor size. We examine the biological plausibility of this association, considering the role of glial fibrillary acidic protein in hepatic stellate cell activation and the growing body of evidence linking citrullination to extracellular matrix remodeling and cancer progression. Additionally, we offer a critical evaluation of the study’s implications, acknowledge its limitations—particularly its retrospective design and the observed discrepancy between OS and recurrence-free survival—and propose a forward-looking research agenda focused on biomarker validation and translational development. The identification of cit-GFAP underscores the matrisome as a promising reservoir of prognostic biomarkers and potential therapeutic targets, thereby advancing the mechanistic understanding of HCC pathogenesis.
Core Tip: This editorial highlights the groundbreaking study by Cho et al that identifies citrullinated glial fibrillary acidic protein (cit-GFAP) as a novel stromal biomarker in hepatocellular carcinoma (HCC). The study shifts the prognostic focus from the tumor cell per se to the post-translationally modified extracellular matrix, demonstrating that elevated cit-GFAP expression is an independent predictor of poor survival following curative resection. We discuss how these findings underscore the critical role of post-translational modifications within the tumor microenvironment and propose a future research agenda for the validation of cit-GFAP and the exploration of peptidylarginine deiminase inhibition as a potential therapeutic strategy in HCC.
