Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival
Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival
复制标题
DOI：
10.3892/or.2013.2675
复制
发表时间：
2013-11-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Dan
中科院分区：
文献类型：
--
作者：
Lu, Guifang;Shan, Tao;Zhang, Dan
着丝粒蛋白H（CENP-H）已被证明在许多类型的癌症中显著上调，并与细胞周期调控，细胞增殖和遗传不稳定性破坏有关。本研究的目的是探讨CENP-H在肝细胞癌（HCC）中的表达和定位，并确定其过表达是否是HCC的预后生物标志物。采用逆转录-聚合酶链反应（PCR）、实时定量PCR和蛋白质印迹法比较HCC样品和相应的相邻非癌样品中CENP-H在mRNA和蛋白质水平上的表达。采用免疫组化法检测60例肝癌组织中CENP-H蛋白的表达，并分析其与临床病理特征及患者预后的关系。此外，进行免疫荧光测定以测试CENP-H蛋白在HCC细胞中的表达和定位。结果显示，CENP-H mRNA和蛋白水平在HCC样品中高于相应的邻近非癌样品。在60对石蜡包埋组织中，CENP-H在HCC样本中上调（38/60，63.3%）相对于相邻的非癌样品（21/60，35%，P=0.003），并且较高水平的上调与肿瘤大小相关结果显示，胃癌的临床分期与病理分级呈正相关（P =0.032），组织学分级越高（P = 0.001），TNM分期越高（P =0.002），中国临床分期越高（P=0.008），预后越差。此外，与IHC的结果一致，免疫荧光测定显示CENP-H定位于Hep 3B细胞的细胞核中。CENP-H在HCC中过表达，其上调水平是独立的预后指标，表明CENP-H可能是治疗HCC的有效治疗策略。
Centromere protein H (CENP-H) has been shown to be significantly upregulated in many types of cancers and is associated with disrupted cell cycle regulation, cell proliferation and genetic instability. The aim of the present study was to explore the expression and localization of CENP-H in hepatocellular carcinoma (HCC) and determine whether its overexpression is a prognostic biomarker for HCC. Reverse transcription-polymerase chain reaction (PCR), real-time qPCR and western blotting were used to compare CENP-H expression at the mRNA and protein levels in HCC samples and corresponding adjacent non-cancerous samples. CENP-H protein levels were determined in 60 paired paraffin-embedded HCC tissues using immunohistochemistry (IHC), and the correlation with clinicopathological features and patient prognosis was analyzed. In addition, an immunofluorescence assay was performed to test the expression and localization of CENP-H protein in HCC cells. Results showed that levels of CENP-H mRNA and protein were higher in HCC samples than in the corresponding adjacent non-cancerous samples. In 60 paired paraffin-embedded tissues, CENP-H was upregulated in the HCC samples (38/60, 63.3%) relative to the adjacent non-cancerous samples (21/60, 35%, P=0.003), and a higher level of upregulation was associated with tumor size (P=0.032); higher histological grade (P=0.001); more advanced TNM stage (P=0.002) and Chinese clinical stage (P=0.008); and poorer prognosis. In addition, consistent with the results of IHC, the immunofluorescence assay showed that CENP-H was localized in the nucleus of Hep3B cells. CENP-H was overexpressed in HCC, and its level of upregulation was an independent prognostic indicator, suggesting that CENP-H may be an effective therapeutic strategy for the treatment of HCC.