Association of Low Zinc Finger Antiviral Protein Expression with Progression and Poor Survival of Patients with Hepatocellular Carcinoma
Association of Low Zinc Finger Antiviral Protein Expression with Progression and Poor Survival of Patients with Hepatocellular Carcinoma
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锌指抗病毒蛋白低表达与肝细胞癌患者进展和不良生存的关系
DOI：
10.1159/000493285
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Peng, Liang
中科院分区：
文献类型：
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作者：
Liu, Ying;Hu, Cheng;Peng, Liang
背景/目的锌指抗病毒蛋白（ZAP）已被报道在肝细胞癌（HCC）中表达，并且ZAP的表达与癌细胞的凋亡信号传导有关。本研究旨在探讨ZAP在HCC细胞中的表达及其临床病理意义。方法采用实时荧光定量PCR和western blot检测正常人肝细胞、肝癌细胞和5种原发性肝癌细胞系中ZAP RNA和蛋白的表达情况。采用免疫组化方法检测147例石蜡包埋的肝癌组织及邻近正常组织中ZAP的表达。分析了ZAP在乙型肝炎病毒（HBV）感染或未感染患者组织样本中表达的临床意义。结果zap在肝癌细胞和人原代肝癌细胞系中的表达明显低于正常人肝细胞。147例HCC样本中，107例（77.0%）HCC组织中ZAP表达低于邻近正常组织。在HCC和HBV感染患者中，ZAP表达与病理分级相关（P< 0.05）；在hbv阴性HCC患者中，ZAP表达与肿瘤大小、临床分期相关（P< 0.05）。ZAP低表达患者的总生存期明显短于ZAP高表达患者的生存期（P< 0.05），特别是中分化至高分化HCC（1-2级）和T1、T2期HCC患者的生存期（P< 0.05）。Cox多因素分析显示，ZAP表达是HCC患者生存的独立预测因子（P< 0.01）。结论ZAP低表达与HCC患者病情进展及预后不良密切相关。
Background/AimsZinc finger antiviral protein (ZAP) has been reported to be expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated with apoptotic signaling in cancer cells. This study aimed at investigating the expression of ZAP in HCC cells and its significance in clinical pathology.MethodsReal-time quantitative PCR and western blot assays were employed to detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The clinical significance of ZAP expression was analyzed in tissue samples from patients with or without infection by hepatitis B virus (HBV).ResultsZAP expression in HCC cells and human primary HCC cell lines was significantly lower than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In patients with HCC and HBV infection, ZAP expression was related to pathological grade (P< 0.05); in HBV-negative patients with HCC, ZAP expression was associated with tumor size (P< 0.05) and clinical stage (P< 0.05). The overall survival time in patients with low ZAP expression was significantly shorter than survival times of those with high ZAP expression (P< 0.05), especially for patients with moderately to well-differentiated HCC (Grade 1–2) and HCC at stage T1 and T2 (P< 0.05). Cox multivariate analysis showed that ZAP expression was an independent predictor of survival of patients with HCC (P< 0.01).ConclusionLow ZAP expression is closely associated with disease progression and poor prognosis for patients with HCC.