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

Table 1 Baseline study characteristics

Ref.	Study design	Sample size	Country	Underlying liver disease	Treatment type	Serum assay	1M2BPGi cutoff	Endpoint	Outcome
Harimoto et al[19], 2022	Two institution retrospective study	60	Japan	HCV-related HCC at SVR	Hepatectomy	Not specified	1.54	RFS	RFS M2BPGi > 1.54. Univariate: HR = 4.67 (1.46-14.92), P < 0.01. Multivariate: HR = 5.54 (1.05-29.14), P = 0.04. Median RFS: High M2BPGi: 1.25 years. Low M2BPGi: Did not reach 50% in 4 years
Yugawa et al[24], 2022	Single-center retrospective study	57	Japan	HCV-related HCC at SVR	Hepatectomy	Lectin-antibody Sandwich Immunoassay (Sysmex Co., Hyogo, Japan)	1.71 COI	RFS	RFS M2BPGi at SVR ≥1.71 COI. Univariate: HR = 3.63 (1.57-8.39), P = 0.0026. Multivariate: HR = 2.98 (1.23-7.19), P = 0.0153. 3/5/7-year RFS: High M2BPGi: 37.3%/12.4%/12.4%. Low M2BPGi: 84.2/84.2%/71.7%
Nanashima et al[15], 2024	Single-center retrospective study	130	Japan	HCC with underlying: Normal liver: 30. MASLD: 44. Primary biliary cholangitis: 2. HBV: 30. HCV: 24	Hepatectomy	Chemiluminescent Enzyme Immunoassay with Anti-Wisteria Floribunda Agglutinin (HSCL-2000i Immunoanalyzer; Sysmex Co., Tokyo, Japan)	1 COI	TFS	TFS 1/3/5 years: < 1 (n = 75) 91/73/65. ≥ 1 (n = 55) 81/66/53. Multi-variate analysis. M2BPGi (COI) (< 1 vs ≥ 1): TFS RR = 1.84 (0.87-3.89), P = 0.11
Lee et al[20], 2025	Single-center retrospective study	247	Taiwan	HCC with underlying: HBV: 107. HCV: 62. HBV + HCV: 3. Nonviral: 75	Hepatectomy	HISCL M2BPGi reagent on HISCL-800 immunoanalyzer (Sysmex Co., Kobe, Japan)	1.5 COI	RFS	RFS M2BPGi (COI). > 1.5 vs ≤ 1.5. Univariate: HR = 1.979 (1.369-2.862), P < 0.001. Multivariate: HR = 2.100 (1.435-3.074), P < 0.001. Median RFS: High M2BPGi: 19.8 months. Low M2BPGi: 56.3 months

¹Cutoff's were derived for each individual study statistically using the receiver operator characteristic, often using Youden Index. However, Nanashima et al[15] utilized company provided data from Sysmex for their cutoff index (COI).

M2BPGi: Mac-2 binding protein glycosylation isomer; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; SVR: Sustained viral response; RFS: Recurrence free survival; HR: Hazard ratio; MASLD: Metabolic dysfunction-associated steatotic liver disease; HBV: Hepatitis B virus; TFS: Tumor free survival; RR: Relative risk.