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

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.