核因子κB在肝癌组织中的表达及其与细胞增殖和凋亡关系

Effects of nuclear factor-κB expression on cell proliferation and apoptosis in hepatocellular carcinoma

目的研究肝细胞癌(hepatocellular carcinoma,HCC)组织中核因子κB(NF-κB)表达水平的变化,分析NF-κB表达与肝癌细胞增殖和凋亡间的相关关系,探讨其表达在临床病理学中的意义。方法应用免疫组织化学法(SP)检测44例HCC组织、25例癌旁相应组织、9例正常肝组织中NF-κB、Ki-67蛋白的表达情况,采用末端脱氧核苷酸转移酶介导的dUTP缺口标记(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法检测细胞凋亡,并计算其增殖指数(PI)和凋亡指数(AI)。结果NF-κB蛋白在HCC组织、癌旁组织中的阳性表达率分别为81.8%(36/44)、28.0%(7/25),9例正常肝组织未见表达,3组比较差异有统计学意义(P<0.01)。在HCC组织中NF-κB表达与组织学分级有关,Ⅲ、Ⅳ级NF-κB表达率显著高于Ⅰ、Ⅱ级(P<0.05),与其他临床病理特征无关。HCC标本中NF-κB阳性表达病例平均PI(29.9±13.7)%,阴性表达者的平均PI(24.2±10.9)%(P>0.05)。HCC标本NF-κB阳性表达者平均AI(2.9±1.4)%,明显低于阴性表达者平均AI(4.9±2.0)%(P<0.05)。结论NF-κB在HCC中高表达,与HCC患者预后相关。NF-κB通过抑制细胞凋亡的方式影响肝癌的生物学特性,而对肝癌的细胞增殖无显著影响。

Objective To investigate the changes of apoptosis inhibitor nuclear factor-κB （NF-κB） in hepatocellular carcinoma（HCC） for the relationship between NF-κB expression and the cell proliferation or apoptosis in HCC,and to explore its clinical significance of pathologic features in patients with HCC. Methods The expressions of NF-κB and Ki-67 protein were tested using immunohistochemistry method（SP）,and the cell apoptosis was detected by terminal deoxynucleotidyl transferase -mediated dUTP nick end labeling（TUNEL） assay in HCC tissues of 44 patients, para-cancerous tissues of 25 patients with HCC and 9 subjects with normal liver. Subsequent proliferation index（PI） and apoptosis index（AI） were calculated. Results The positive rate of NF-κB protein in 44 HCC tissues was 81.8% （36/44） ,compared with 28.0% （7/25） in para-cancerous tissues, and none in normal liver tissues（ P 〈0.01）. The expression of NF-κB in HCC was correlated to histological differentiation,of which Ⅲ,Ⅳ were higher than Ⅰ , Ⅱ （ P 〈 0.05） ,but not correlated with other clinical pathologic features of the patients with HCC. The average value of PI in NF-κB positive cases in HCC was （29.9±13.7）%,and （24.2±10.9）% in negative cases（ P 〉0.05）. The average value of AI in NF-κB positive cases in HCC was （ 2.9± 1.4） %, and （4.9 ±2.0） % in negative cases （ P 〈 0.05 ）. Conclusion The high expression of NF-κB values in judging the prognosis of HCC patients. NF-κB plays an important role in the cell apoptosis and does not significantly influence the cell progression of HCC.