Clinical significance of increased expression of Nijmegen breakage syndrome gene (NBS1) in human primary liver cancer
Clinical significance of increased expression of Nijmegen breakage syndrome gene (NBS1) in human primary liver cancer
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DOI：
10.1007/s12072-013-9500-x
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发表时间：
2014-04-01
影响因子：
6.6
通讯作者：
Huang, Jian
中科院分区：
文献类型：
--
作者：
Wang, Yan;Li, Man;Huang, Jian
作为维持基因组不稳定所必需的DNA修复相关基因，奈梅根断裂综合征基因(NBS1)编码一种蛋白质Nbs1(P95/Nibrin)，参与DNA双链断裂的处理/修复。为探讨Nbs1在人原发性肝癌(包括乙肝病毒相关性肝细胞癌和肝内胆管细胞癌)中的分子变化，采用免疫组织化学、实时荧光定量RT-PCR和免疫印迹方法检测了110例原发性肝癌组织中Nbs1的表达水平。通过检测Ki-67抗原阳性细胞百分率和组蛋白磷酸化H_2AX(Gamma-H_2AX)水平来评价NBS1表达与肝癌细胞增殖和DNA损伤程度的关系。冰冻组织和石蜡切片检测到54.6%和47.3%的肝细胞癌组织中NBS1表达高于相应的癌旁组织。Nbs1在低分化肝细胞癌(p=0.0265)和所有低分化ICC中表达增高的频率较高，提示Nbs1表达增高与肝癌细胞的恶性程度有关。此外，肝细胞癌组织中Ki-67阳性细胞百分率和γ-H_2AX表达水平与Nbs1表达水平呈正相关，提示Nbs1表达增强的增殖期肝癌细胞存在DNA损伤反应，Nbs1表达增强可能在肝癌的发生发展中起重要作用，NBS1表达状态可能有助于评估原发性肝癌的恶性程度。
As a DNA repair-associated gene essential for maintaining genomic instability, Nijmegen breakage syndrome gene (NBS1), codes for a protein, Nbs1(p95/Nibrin), involved in the processing/repair of DNA double-strand breaks. The aim of this study is to investigate the molecular alteration of Nbs1 in human primary liver cancer, including HBV-associated hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).The expression levels of Nbs1 in 110 cases of primary liver cancer, including 85 HCCs and 25 ICCs, were detected by immunohistochemistry, real-time RT-PCR and Western blot analysis. The percentage of Ki-67 antigen-positive cells and the level of phosphorylated histone H2AX (gamma-H2AX) were detected to evaluate the relationship of Nbs1 expression with proliferation and the degree of DNA damage in HCC cells.Increased Nbs1 expression was observed in tumor compared to corresponding adjacent non-tumor tissue in 54.6 and 47.3 % of HCC cases detected with frozen tissues and paraffin sections. Higher frequency of increased Nbs1 expression was shown in poorly differentiated HCCs (p = 0.0265) and in all poorly differentiated ICCs, indicating the increased Nbs1 expression is associated with the degree of malignancy of HCC cells. Moreover, the percentage of Ki-67-positive cells and the level of gamma-H2AX correlate well with increased Nbs1 expression in HCC cases, suggesting an activated DNA damage response in proliferating HCC cells with increased Nbs1 expression.Increased Nbs1 expression might play a significant role in liver cancer progression, and the status of Nbs1 expression might be helpful for evaluation of the degree of malignancy of primary liver cancer.