Stephens KR, Wilson M, Xu M, Gaskins JT, Genova G, Martin II RCG. Mac-2 binding protein glycosylation isomer as a novel serum biomarker for recurrence in hepatocellular carcinoma. World J Gastroenterol 2026; 32(5): 113693 [DOI: 10.3748/wjg.v32.i5.113693]
Corresponding Author of This Article
Robert C G Martin II, MD, PhD, Division of Surgical Oncology, Hiram C Polk Jr, MD, Department of Surgery, University of Louisville, 315 E Broadway, Louisville, KY 40202, United States. robert.martin@louisville.edu
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Surgery
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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/
Feb 7, 2026 (publication date) through Jan 28, 2026
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World Journal of Gastroenterology
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1007-9327
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Stephens KR, Wilson M, Xu M, Gaskins JT, Genova G, Martin II RCG. Mac-2 binding protein glycosylation isomer as a novel serum biomarker for recurrence in hepatocellular carcinoma. World J Gastroenterol 2026; 32(5): 113693 [DOI: 10.3748/wjg.v32.i5.113693]
World J Gastroenterol. Feb 7, 2026; 32(5): 113693 Published online Feb 7, 2026. doi: 10.3748/wjg.v32.i5.113693
Mac-2 binding protein glycosylation isomer as a novel serum biomarker for recurrence in hepatocellular carcinoma
Kyle R Stephens, Megan Wilson, Manting Xu, Jeremy T Gaskins, Gina Genova, Robert C G Martin II
Kyle R Stephens, Megan Wilson, Robert C G Martin II, Division of Surgical Oncology, Hiram C Polk Jr, MD, Department of Surgery, University of Louisville, Louisville, KY 40202, United States
Manting Xu, Department of Radiology, University of Louisville, Louisville, KY 40202, United States
Jeremy T Gaskins, Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, United States
Gina Genova, Kornhauser Health Sciences Library, University of Louisville, Louisville, KY 40202, United States
Co-first authors: Kyle R Stephens and Megan Wilson.
Author contributions: Stephens KR and Wilson M are co-first authors, and contributed equally to study conception, protocol design, data extraction, and drafting of the manuscript. Martin II RCG is the corresponding author who supervised the study, provided critical revisions, and is responsible for the overall integrity of the work as the corresponding author. Gaskins JT conducted the statistical analyses, generated the figures, and contributed to interpretation of the data. Genova G designed and executed the systematic search strategy across all databases and assisted with reference management. Xu M assisted with screening of articles, data verification, and formatting of figures and tables. All authors reviewed and approved the final manuscript.
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: Robert C G Martin II, MD, PhD, Division of Surgical Oncology, Hiram C Polk Jr, MD, Department of Surgery, University of Louisville, 315 E Broadway, Louisville, KY 40202, United States. robert.martin@louisville.edu
Received: September 1, 2025 Revised: October 31, 2025 Accepted: December 22, 2025 Published online: February 7, 2026 Processing time: 149 Days and 20.5 Hours
Abstract
BACKGROUND
Accurate prediction of hepatocellular carcinoma (HCC) recurrence after curative therapy remains challenging. Mac-2 binding protein glycosylation isomer (M2BPGi), a serum marker of liver fibrosis, may serve as a noninvasive prognostic biomarker.
AIM
To evaluate the association between preoperative M2BPGi levels and HCC recurrence following curative treatment.
METHODS
We searched PubMed Cochrane CENTRAL, EMBASE, and BIOSIS Citation Index for English-language studies in humans reporting HCC recurrence outcomes stratified by high vs low serum M2BPGi. Four retrospective studies (total n = 494) met inclusion criteria for meta-analysis. Data on recurrence-related survival (recurrence-free, tumor-free, or progression-free survival) and unadjusted and/or adjusted hazard ratios (HR) for high vs low M2BPGi were extracted. Random-effects meta-analyses were performed separately for univariate and multivariate HRs. Heterogeneity was assessed by I2 and publication bias by Egger’s test.
RESULTS
High preoperative M2BPGi was significantly associated with increased recurrence risk. The pooled unadjusted HR was 2.98 (95%CI: 1.50-5.91; P < 0.01; I2 = 38.3%), and the pooled adjusted HR was 2.22 (95%CI: 1.48-3.32; P < 0.01; I2 = 0%). Meta-regression showed no effect of varying cutoff thresholds on HRs, and Egger’s tests indicated no evidence of publication bias in the multivariate results. The bias-corrected estimated of the univariate HR remained statistically significant (HR = 2.31, 95%CI: 1.21-4.41, P = 0.021, I2 = 32%).
CONCLUSION
Preoperative serum M2BPGi is a promising biomarker for HCC recurrence after hepatectomy. Its strong association with risk, minimal heterogeneity across studies, and ease of measurement support its potential clinical utility.
Core Tip: Predicting tumor recurrence following curative treatment for hepatocellular carcinoma (HCC) remains a challenging task. Numerous novel biomarkers have been investigated for their ability to predict disease prognosis, as there is a clear need for noninvasive serum assays that can reliably assess the risk for post-treatment recurrence. Mac-2 binding protein glycosylation isomer (M2BPGi) has emerged as a serum biomarker for liver fibrosis, an important component of HCC pathogenesis. Our meta-analysis demonstrates M2BPGi’s utility as a pre-operative predictor of HCC recurrence.
