Hu Ben-Shun, Zhao Gang, Yu Hai-Feng, Chen Ke, Dong Jia-Hong, Tan Jing-Wang
Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Tumour Biol. 2013 Feb;34(1):271-6. doi: 10.1007/s13277-012-0547-4. Epub 2012 Oct 5.
The aim of this study was to evaluate the association between activating enhancer binding protein 4 (AP-4) tissue expression and patient prognosis in hepatocellular carcinoma (HCC). The levels of AP-4 mRNA and protein in tumor and para-tumor tissue were evaluated in 30 HCC cases by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Additionally, AP-4 protein expression in 112 HCC was analyzed by immunohistochemistry. The correlation of AP-4 expression and patients' clinicopathological parameters was evaluated. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. By RT-PCR and Western blot, the levels of AP-4 mRNA and protein were significantly higher in HCC, compared to that in para-tumor tissue (p < 0.001). Immunohistochemical staining revealed that AP-4 was highly expressed in 53.6 % of the HCC patients. The AP-4 expression level was closely associated with serum alpha fetoprotein elevation, tumor size, histological differentiation, tumor recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis showed that a high expression level of AP-4 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that AP-4 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that a high expression level of AP-4 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that AP-4 may be a potential target of antiangiogenic therapy for HCC.
本研究旨在评估激活增强子结合蛋白4（AP-4）的组织表达与肝细胞癌（HCC）患者预后之间的关联。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法，对30例HCC病例的肿瘤组织和癌旁组织中AP-4的mRNA和蛋白水平进行了评估。此外，采用免疫组织化学方法分析了112例HCC中AP-4蛋白的表达情况，并评估了AP-4表达与患者临床病理参数之间的相关性。使用Kaplan-Meier法和Cox比例风险模型进行生存分析。通过RT-PCR和蛋白质免疫印迹法发现，与癌旁组织相比，HCC中AP-4的mRNA和蛋白水平显著更高（p < 0.001）。免疫组织化学染色显示，53.6%的HCC患者中AP-4呈高表达。AP-4表达水平与血清甲胎蛋白升高、肿瘤大小、组织学分化、肿瘤复发、肿瘤转移及肿瘤分期密切相关。Kaplan-Meier生存分析表明，AP-4高表达导致HCC患者预后显著较差。多因素分析显示，AP-4表达水平是HCC患者总生存率的独立预后参数。这些研究结果表明，AP-4高表达可作为HCC预后不良的生物标志物。因此，我们推测AP-4可能是HCC抗血管生成治疗的潜在靶点。
