Mac-2 binding protein glycosylation isomer as a novel serum biomarker for recurrence in hepatocellular carcinoma

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 I 2 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; I 2 = 38.3%), and the pooled adjusted HR was 2.22 (95%CI: 1.48-3.32; P < 0.01; I 2 = 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, I 2 = 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.