Background: Glypican-3 (GPC3) is overexpressed in most hepatocellular carcinoma (HCC) tissues but is absent in normal adult liver. We evaluated whether tumor GPC3 expression is associated with clinical outcomes in patients with advanced HCC treated with atezolizumab–bevacizumab (AB).Methods: We conducted a single-center retrospective cohort study of 139 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who received AB between January 2022 and August 2025. Tumor GPC3 expression was assessed by immunohistochemistry. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST).Results: Baseline characteristics were largely balanced between GPC3-positive (n = 87) and GPC3-negative (n = 52) groups. Median OS was significantly shorter in patients with GPC3-positive tumors than in those with GPC3-negative tumors (p= 0.006). In multivariable analysis, GPC3 positivity remained independently associated with higher mortality (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.05–3.00;p= 0.033), along with Child–Pugh class B. PFS did not differ significantly between the groups (p= 0.712). ORR was lower in GPC3-positive tumors than in GPC3-negative tumors (approximately 17–18% vs. ~32%;p= 0.023). Membranous GPC3 localization was associated with inferior OS compared with cytoplasmic or absent expression (p= 0.025).Conclusions: Tumor GPC3 expression was associated with decreased OS and lower ORR among AB-treated patients with advanced HCC, suggesting potential clinical relevance and may help in risk stratification.
背景：磷脂酰肌醇蛋白聚糖-3（GPC3）在大多数肝细胞癌（HCC）组织中过表达，但在正常成人肝脏中不表达。本研究旨在评估接受阿特珠单抗-贝伐珠单抗（AB）联合治疗的晚期HCC患者中，肿瘤GPC3表达是否与临床结局相关。 方法：我们开展了一项单中心回顾性队列研究，纳入2022年1月至2025年8月期间接受AB治疗的139例巴塞罗那临床肝癌（BCLC）C期HCC患者。通过免疫组织化学检测肿瘤GPC3表达。主要终点为总生存期（OS）和无进展生存期（PFS），次要终点为基于实体瘤疗效评价标准修订版（mRECIST）的客观缓解率（ORR）。 结果：GPC3阳性组（n=87）与GPC3阴性组（n=52）的基线特征基本平衡。GPC3阳性肿瘤患者的中位OS显著短于GPC3阴性患者（p=0.006）。多变量分析显示，GPC3阳性与Child-Pugh B级均为死亡风险增加的独立相关因素（风险比[HR] 1.77，95%置信区间[CI] 1.05–3.00；p=0.033）。两组间PFS无显著差异（p=0.712）。GPC3阳性肿瘤的ORR低于GPC3阴性肿瘤（约17–18% vs. 约32%；p=0.023）。与胞质表达或不表达相比，GPC3膜定位与较差的OS相关（p=0.025）。 结论：在AB治疗的晚期HCC患者中，肿瘤GPC3表达与OS缩短及ORR降低相关，提示其具有潜在的临床相关性，可能有助于风险分层。
肿瘤(癌症)患者之家