肝癌癌旁组织中FGL1的表达特征及其与预后的关系

Expression characteristics of FGL1 in peritumoral tissues of hepatocellular carcinoma and its association with prognosis

摘要:

背景与目的 肝癌具有高度异质性，现有预后模型预测能力有限。纤维蛋白原相关蛋白1（FGL1）是肝脏特异性分泌蛋白，也是淋巴细胞激活基因3（LAG-3）的重要配体，其在肿瘤免疫调控中的作用日益受到关注。本研究旨在评估癌旁组织中FGL1的表达特征及其对肝癌术后预后的预测价值。方法 回顾性纳入2010年1月─2013年12月在复旦大学附属华山医院接受根治性切除的183例肝癌患者。采用免疫组织化学法检测癌旁组织及癌组织中FGL1表达水平，并以H-score进行定量。同时结合TCGA数据库验证表达趋势。通过最大选择秩统计量法确定FGL1表达截断值，比较癌旁FGL1高、低表达患者的生存差异，采用Cox比例风险模型评估独立预后因素。结果 TCGA数据及临床样本均显示，癌旁组织中FGL1表达明显高于癌组织（均P<0.05）。根据最佳截断值将患者分为高表达组与低表达组。高表达组5年无病生存（DFS）率和总体生存（OS）率均显著低于低表达组（均P<0.05）。多因素Cox回归分析显示，癌旁FGL1高表达是DFS（HR=1.689，95% CI=1.010~2.823，P=0.046）和OS（HR=1.733，95% CI=1.112~2.702，P=0.015）的独立危险因素。结论 癌旁组织FGL1表达显著高于肿瘤组织，其高表达与肝癌术后复发及生存不良密切相关。癌旁FGL1可能作为独立预后生物标志物，并为靶向FGL1/LAG-3轴的免疫治疗策略提供潜在依据。

Abstract:

Background and Aims Liver cancer exhibits marked biological heterogeneity, and reliable prognostic biomarkers remain limited. Fibrinogen-like protein 1 (FGL1), a liver-specific secreted protein and a major ligand of lymphocyte activation gene 3 (LAG-3), has emerged as a critical regulator of tumor immunity. This study aimed to evaluate the expression pattern of FGL1 in peritumoral tissues and its prognostic significance in liver cancer patients after curative resection.Methods A total of 183 patients with liver cancer who underwent curative resection at Huashan Hospital, Fudan University, between January 2010 and December 2013 were retrospectively collected. FGL1 expression levels in peri-tumoral and tumor tissues were detected by immunohistochemistry and quantified using the H-score method. Expression patterns were further validated using data from The Cancer Genome Atlas (TCGA) database. The optimal cutoff value for FGL1 expression was determined using maximally selected rank statistics. Survival differences between patients with high and low peritumoral FGL1 expression were compared, and independent prognostic factors were evaluated using Cox proportional hazards regression models.Results Both TCGA data and clinical samples demonstrated significantly higher FGL1 expression in peritumoral tissues compared with tumor tissues (both P<0.05). Patients were stratified into high- and low-expression groups based on the optimal cutoff value. High peritumoral FGL1 expression was significantly associated with poorer disease-free survival (DFS) and overall survival (OS) rates (both P<0.05). Multivariate Cox analysis identified peritumoral FGL1 overexpression as an independent predictor of DFS (HR=1.689, 95% CI=1.010-2.823, P=0.046) and OS (HR=1.733, 95% CI=1.112-2.702, P=0.015).Conclusion FGL1 expression is significantly elevated in peritumoral tissues of HCC and independently predicts unfavorable postoperative outcomes. Peri-tumoral FGL1 may serve as a novel prognostic biomarker and a potential therapeutic target in the FGL1/LAG-3 immune axis.