The Overexpression of CCAR1 in Hepatocellular Carcinoma Associates with Poor Prognosis.
The Overexpression of CCAR1 in Hepatocellular Carcinoma Associates with Poor Prognosis.
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DOI：
10.4143/crt.2015.302
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发表时间：
2016-07
影响因子：
4.6
通讯作者：
Park CK
中科院分区：
文献类型：
--
作者：
Ha SY;Kim JH;Yang JW;Kim J;Kim B;Park CK
细胞分裂周期和凋亡调节因子1（CCAR 1）在包括不同癌细胞在内的多种细胞类型中作为类固醇/甲状腺核受体、β-连环蛋白和p53的辅因子，在调节细胞生长和凋亡中发挥动态作用。然而，CCAR 1蛋白是否在肝细胞癌（HCC）中过表达以及CCAR 1蛋白表达在HCC中的预后意义尚未见报道。采用免疫组化方法检测167例长期随访的HCC患者中CCAR 1蛋白的表达。CCAR 1蛋白在167例HCC中有149例（89.2%）高表达，与微血管浸润、肝内转移、美国癌症联合委员会（AJCC）较高的T分期和早期复发显著相关。CCAR 1高表达对无复发生存期（RFS）有不利影响（p=0.002）。在亚组分析中，在甲胎蛋白≤ 20 ng/mL的患者（n=54）和AJCC T 1期患者（n=62）中，观察到CCAR 1高表达组和CCAR 1低表达组之间的RFS存在显著差异（分别为p=0.015和p=0.004）。CCAR 1高表达倾向于成为较短RFS的独立预测因子（p=0.054），并显示对总生存期（OS）的不利影响（p=0.015）。在亚组分析中，在甲胎蛋白≤ 20 ng/mL的患者中（n=54），观察到CCAR 1高表达组和CCAR 1低表达组之间的OS差异有统计学意义（p=0.046）。CCAR 1蛋白可能是预测肝癌患者根治性肝切除术后RFS的潜在生物标志物。此外，CCAR 1在血清甲胎蛋白水平正常的HCC患者或早期HCC中具有预后价值。
Cell division cycle and apoptosis regulator 1 (CCAR1) plays a dynamic role in regulation of cell growth and apoptosis by serving as a cofactor of steroid/thyroid nuclear receptors, β-catenin, and p53 in a variety of cell types including different cancer cells. However, whether CCAR1 protein is overexpressed in hepatocellular carcinoma (HCC) and the prognostic significance of CCAR1 protein expression in HCC have not been reported. In 167 HCC patients with long-term follow-up, CCAR1 protein expression was examined by immunohistochemistry. High CCAR1 protein expression was observed in 149 of the 167 HCC cases (89.2%) and showed significant correlation with microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T stage, and early recurrence. High CCAR1 expression showed an unfavorable effect on recurrence-free survival (RFS) (p=0.002). In subgroup analysis, among patients with α-fetoprotein ≤ 20 ng/mL (n=54) and patients with AJCC T stage 1 (n=62), significant differences in RFS were observed between high CCAR1 expression groups and low CCAR1 expression groups (p=0.015 and p=0.004, respectively). High CCAR1 expression tended to be an independent predictor of shorter RFS (p=0.054) and showed an unfavorable effect on overall survival (OS) (p=0.015). In subgroup analysis, among patients with α-fetoprotein ≤ 20 ng/mL (n=54), significant difference in OS was observed between high CCAR1 expression group and low CCAR1 expression group (p=0.046). CCAR1 protein could be a potential biomarker predicting RFS in HCC patients after curative hepatectomy. In addition, CCAR1 had prognostic values in HCC patients with normal serum α-fetoprotein levels or early stage HCC.