Glypican-3在乙型肝炎病毒相关性肝细胞癌肝移植患者中的预后价值。
Prognostic value of glypican-3 in patients with HBV-associated hepatocellular carcinoma after liver transplantation.
作者信息
Cui Xiao, Li Zhao, Gao Peng-Ji, Gao Jie, Zhu Ji-Ye
机构信息
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
出版信息
Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):157-63. doi: 10.1016/s1499-3872(15)60349-6.
BACKGROUND
Glypican-3 (GPC-3) is frequently overexpressed in hepatocellular carcinoma (HCC). Recent studies have shown that GPC-3 is a highly efficient diagnostic biomarker of HCC and an indicator of poor prognosis in HCC patients who have undergone hepatectomy. However, its prognostic value in patients with HBV-associated HCC after liver transplantation (LT) is not clear. The present study is to evaluate the prognostic value of GPC-3 in patients with HBV-associated HCC after LT.
METHODS
A cohort of 104 HCC patients with HBV-associated cirrhosis who had undergone LT at our hospital between 2002 and 2011 were enrolled in this study. Samples of HCC were taken from these patients. GPC-3 protein expression was detected in paraffin-embedded specimens using immunohistochemistry. All related clinical data were obtained from the China Liver Transplant Registry. The relationship between GPC-3 expression and clinicopathological parameters was analyzed. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis.
RESULTS
GPC-3 was expressed in samples from 74 (71.2%) of the 104 patients. GPC-3 was expressed only in HCC cells. Positive staining was correlated with tumor size (P=0.004), encapsulation (P=0.018), pathological stage (P=0.027), portal vein invasion (P=0.043), tumor differentiation (P=0.002) and the Milan criteria (P=0.016). The 5-year survival rate and disease-free survival rate of patients with GPC-3-positive were lower than those (38.2% vs 75.4%, P<0.001; 30.8% vs 69.7%, P=0.001) of patients with GPC-3-negative. Multivariate Cox-regression analysis revealed that GPC-3 was an independent risk factor for 5-year survival rate (P=0.031) and disease-free survival rate (P=0.047), together with tumor differentiation, Milan criteria and pre-operative alpha-fetoprotein.
CONCLUSION
GPC-3 is a potential biomarker for poor prognosis after LT in HCC patients with HBV-associated cirrhosis.
背景
磷脂酰肌醇蛋白聚糖-3（GPC-3）在肝细胞癌（HCC）中经常过度表达。最近的研究表明，GPC-3是HCC的一种高效诊断生物标志物，也是接受肝切除的HCC患者预后不良的指标。然而，其在肝移植（LT）后乙肝相关HCC患者中的预后价值尚不清楚。本研究旨在评估GPC-3在LT后乙肝相关HCC患者中的预后价值。
方法
本研究纳入了2002年至2011年期间在我院接受LT的104例乙肝相关肝硬化HCC患者队列。从这些患者中获取HCC样本。使用免疫组织化学检测石蜡包埋标本中的GPC-3蛋白表达。所有相关临床数据均来自中国肝移植登记处。分析GPC-3表达与临床病理参数之间的关系。采用单因素和多因素Cox回归分析确定预后不良的危险因素。
结果
104例患者中74例（71.2%）的样本中检测到GPC-3表达。GPC-3仅在HCC细胞中表达。阳性染色与肿瘤大小（P=0.004）、包膜（P=0.018）、病理分期（P=0.027）、门静脉侵犯（P=0.043）、肿瘤分化（P=0.002）和米兰标准（P=0.016）相关。GPC-3阳性患者的5年生存率和无病生存率低于GPC-3阴性患者（38.2%对75.4%；P<0.001；30.8%对69.7%；P=0.001）。多因素Cox回归分析显示，GPC-3是5年生存率（P=0.031）和无病生存率（P=0.047）的独立危险因素，同时还有肿瘤分化、米兰标准和术前甲胎蛋白。
结论
GPC-3是乙肝相关肝硬化HCC患者LT后预后不良的潜在生物标志物。
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