Clinical relevance of serum full-length glypican-3 in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab

Abstract Biomarkers that can predict patient survival and the therapeutic response to atezolizumab and bevacizumab (Atezo/Bev) as first-line chemotherapy for unresectable hepatocellular carcinoma (HCC) have yet to be identified. We aimed to determine whether the serum full-length glypican-3 (FL-GPC3) concentration can be used as such a biomarker. We included 102 patients treated with Atezo/Bev therapy for unresectable HCC at our institute during 2020–2025. We investigated the association between baseline serum FL-GPC3 concentrations and the therapeutic effectiveness and survival outcomes. The baseline serum FL-GPC3 concentration was lower in patients in whom disease control was achieved (10.8 vs. 26.7 pg/mL, p = 0.002). An FL-GPC3 concentration ≥ 21.7 pg/mL was an independent negative predictor of disease control (odds ratio, 0.382; 95% confidence interval [CI], 0.151–0.970; p = 0.043). The FL-GPC3-high group had a shorter median progression-free survival (PFS; 3.0 vs. 5.6 months, p = 0.031) and overall survival (OS; 13.7 vs. 25.8 months, p = 0.006) than the FL-GPC3-low group. A high FL-GPC3 concentration was an independent negative prognostic factor for PFS (hazard ratio [HR], 1.592; 95% CI, 1.041–2.435; p = 0.032) and OS (HR, 1.807; 95% CI, 1.084–3.012; p = 0.023). In conclusion, the serum FL-GPC3 concentration may serve as a noninvasive prognostic biomarker in patients with HCC treated with immunotherapy.