GPC3作为肝癌预后指标和免疫治疗新靶点的研究进展

The research progress of GPC3 as a prognostic index and promising immunotherapy target for hepatocellular carcinoma

磷脂酰肌醇蛋白聚糖-3(glypican-3,GPC3)是硫酸乙酰肝素糖蛋白(heparan sulfate proteoglycans,HSPGs)家族中的一员,它的成员通过糖基磷脂酰肌醇锚(glycosylphosphatidylinositol,GPI)连接于细胞表面。GPC3在胎儿肝脏中含量丰富,而在成人肝脏中几乎不表达。值得注意的是GPC3在肝细胞癌(hepatocellular carcinoma,HCC)中高表达,同时一些研究结果表明GPC3过表达的HCC患者预后较差。目前,一些关于靶向GPC3免疫治疗的研究已取得一定的成果,例如人源化抗-GPC3单克隆抗体,肽疫苗和免疫毒素治疗。因此,GPC3有望成为分子标记物并用于HCC的诊断,可作为靶点用于HCC的干预治疗,也可为判断预后情况提供一项指标。本文总结当前的一些研究,说明在HCC治疗过程中检测GPC3及其靶向作用具有重要的临床意义。

Glypican-3（ GPC3） is a family of heparan sulfate proteoglycans（ HSPGs） whose members are bound to the cell surface by glycosylphosphatidylinositol（ GPI）. GPC3 is abundant in fetal liver,but its expression is hardly detectable in adult liver. Importantly,GPC3 is overexpressed in hepatocellular carcinoma（ HCC）,and some studies reported that its overexpression predicts a poorer prognosis for HCC patients. At present,some studies on GPC3-targeting immunotherapy are under investigations,such as humanized anti-GPC3 monoclonal antibody,peptide vaccine and immunotoxin therapies. Therefore,GPC3 is not only expected to be a useful molecular marker for the diagnosis of HCC,and can be used as a target for therapeutic intervention in HCC,but also provide an index for assessing the prognosis. This review summarizes some current studies in order to illustrate GPC3 detection and its targeting have important clinical value in the treatment with HCC.