磷脂酰肌醇蛋白聚糖-3是肝细胞癌的一个预后因素和免疫治疗靶点。
Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma.
作者信息
Haruyama Yukihiro, Kataoka Hiroaki
机构信息
Yukihiro Haruyama, Hiroaki Kataoka, Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
出版信息
World J Gastroenterol. 2016 Jan 7;22(1):275-83. doi: 10.3748/wjg.v22.i1.275.
Glypican-3 (GPC3) is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol. Whereas GPC3 is abundant in fetal liver, its expression is hardly detectable in adult liver. Importantly, GPC3 is overexpressed in hepatocellular carcinoma (HCC), and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients. Therefore, GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC. Indeed, some immunotherapy protocols targeting GPC3 are under investigations; those include humanized anti-GPC3 cytotoxic antibody, peptide vaccine and immunotoxin therapies. When considering the clinical requirements for GPC3-targeting therapy, companion diagnostics to select the appropriate HCC patients are critical, and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose. This review summarizes current knowledge regarding the clinical implication of GPC3 detection and targeting in the management of patients with HCC.
磷脂酰肌醇蛋白聚糖-3（GPC3）是一种细胞表面的癌胚蛋白聚糖，通过糖基磷脂酰肌醇锚定。GPC3在胎儿肝脏中含量丰富，而在成人肝脏中几乎检测不到其表达。重要的是，GPC3在肝细胞癌（HCC）中过度表达，多项免疫组织化学研究报告称，其过度表达预示着HCC患者的预后较差。因此，GPC3可作为HCC诊断的有用分子标志物，也可作为HCC治疗干预的靶点。事实上，一些针对GPC3的免疫治疗方案正在研究中；这些方案包括人源化抗GPC3细胞毒性抗体、肽疫苗和免疫毒素疗法。在考虑GPC3靶向治疗的临床需求时，选择合适的HCC患者的伴随诊断至关重要，为此已建议对组织切片进行免疫组织化学分析和检测血清GPC3水平。本综述总结了目前关于GPC3检测及靶向治疗在HCC患者管理中的临床意义的知识。
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