Lee I-Cheng, Lei Hao-Jan, Wang Lei-Chi, Yeh Yi-Chen, Chau Gar-Yang, Hsia Cheng-Yuan, Chou Shu-Cheng, Luo Jiing-Chyuan, Hou Ming-Chih, Huang Yi-Hsiang
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Liver Cancer. 2024 Aug 14;14(1):68-79. doi: 10.1159/000540802. eCollection 2025 Mar.
Novel biomarkers reflecting liver fibrosis and the immune microenvironment may correlate with the risk of hepatocellular carcinoma (HCC) recurrence. This study aimed to evaluate the prognostic value of serum biomarkers in predicting HCC recurrence.
Serum biomarkers, including M2BPGi, IL-6, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3, were measured in 247 patients with HCC undergoing surgical resection. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated. The ERASL-post model and IMbrave050 criteria were used to define HCC recurrence risk groups.
Serum M2BPGi levels significantly correlated with FIB-4 score, aspartate transaminase-to-platelet ratio index, ALBI score, alpha-fetoprotein (AFP), alanine transaminase, aspartate transaminase, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3 levels. M2BPGi, VEGF-A, soluble PD-1, and TIM-3 levels significantly correlated with RFS. In multivariate analysis, M2BPGi >1.5 COI (hazard ratio [HR] = 2.100, < 0.001), tumor size >5 cm (HR = 1.859, = 0.002), multiple tumors (HR = 2.562, < 0.001), AFP >20 ng/mL (HR = 2.141, < 0.001), and microvascular invasion (HR = 1.954, = 0.004) were independent predictors of RFS. M2BPGi levels significantly stratified the recurrence risk in ERASL-post and IMbrave050 risk groups. An M2BPGi-based model could significantly discriminate RFS in the overall cohort as well as in the IMbrave050 low- and high-risk groups. M2BPGi >1.5 COI was also an independent predictor of OS after resection (HR = 2.707, < 0.001).
Serum M2BPGi levels significantly correlated with surrogate markers of liver fibrosis, liver function, and immunology. M2BPGi is a significant predictor of HCC recurrence and survival after resection and could be incorporated into recurrence-prediction models.
反映肝纤维化和免疫微环境的新型生物标志物可能与肝细胞癌（HCC）复发风险相关。本研究旨在评估血清生物标志物在预测HCC复发中的预后价值。
对247例行手术切除的HCC患者检测血清生物标志物，包括M2BPGi、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、趋化因子配体5（CCL5）、血管内皮生长因子A（VEGF-A）、可溶性程序性死亡受体1（sPD-1）、程序性死亡受体配体1（PD-L1）、T细胞免疫球蛋白黏蛋白分子3（TIM-3）和淋巴细胞激活基因3（LAG-3）。评估与无复发生存期（RFS）和总生存期（OS）相关的因素。采用欧洲肝脏病研究学会-术后（ERASL-post）模型和IMbrave050标准定义HCC复发风险组。
血清M2BPGi水平与FIB-4评分、天冬氨酸转氨酶与血小板比值指数、白蛋白-胆红素（ALBI）评分、甲胎蛋白（AFP）、丙氨酸转氨酶、天冬氨酸转氨酶、IL-10 、CCL5、VEGF-A、sPD-1、PD-L1、TIM-3和LAG-3水平显著相关。M2BPGi、VEGF-A、sPD-1和TIM-3水平与RFS显著相关。多因素分析显示，M2BPGi>1.5 COI（风险比[HR]=2.100，P<0.001）、肿瘤大小>5 cm（HR=1.859，P=0.002）、多发肿瘤（HR=2.562，P<0.001）、AFP>20 ng/mL（HR=2.141，P<0.001）和微血管侵犯（HR=1.954，P=0.004）是RFS的独立预测因素。M2BPGi水平在ERASL-post和IMbrave050风险组中对复发风险进行了显著分层。基于M2BPGi的模型能够显著区分整个队列以及IMbrave050低风险和高风险组中的RFS。M2BPGi>1.5 COI也是切除术后OS的独立预测因素（HR=2.707，P<0.001）。
血清M2BPGi水平与肝纤维化、肝功能和免疫学替代标志物显著相关。M2BPGi是HCC切除术后复发和生存的重要预测指标，可纳入复发预测模型。
