Survivin,Caspase-3蛋白在原发性肝癌中的表达及意义

Expression of Survivin and Caspase-3 in Human Hepatocellular Carcinoma

目的:研究原发性肝癌组织及癌旁组织中survivin、caspase3的表达及其与细胞凋亡的关系。方法:收集原发性肝癌组织及相应癌旁组织标本40例,免疫组织化学方法检测其survivin、caspase3蛋白表达,原位末端转移酶标记(TUNEL)法检测凋亡指数。结果:85%(34/40)的肝癌组织表达survivin蛋白,而癌旁非肝癌组织内无1例呈阳性表达。survivin蛋白表达的阳性率在肝内转移者为93.5%,显著高于无肝内转移者(55.6%,P<0.05);在门静脉癌栓浸润者为92.8%,显著高于无门静脉癌栓浸润者(66.7%,P<0.05)。37.5%(15/40)的肝癌组织内可见到caspase3阳性表达,77.5%(31/40)癌旁组织可见不同程度caspase3阳性表达,两者比较差异有显著性意义(P<0.05)。所有肝癌组织标本中均可检测到凋亡细胞,但survivin表达阳性者的凋亡指数(1.152%±0.326%)显著低于survivin表达阴性者(4.502%±0.830%,P<0.05);而caspase3表达阴性者的凋亡指数(5.016%±0.370%)显著高于caspase3表达阴性者(1.927%±0.237%,P<0.05)。34例survivin表达阳性组织中有10例见caspase3表达阳性(29.4%),而6例survivin表达阴性组织中有5例见caspase3阳性表达(83.3%),两者比较差异有显著性意义(P<0.05)。结论:survivin在肝癌组织中选择性表达,与肿瘤转移、血管浸润等恶性生物学行为有关,survivin对凋亡的抑制可能是其参与肝癌发生的重要机制,其作用机制可能涉及到caspase3蛋白的抑制。

Objective： To investigate the role of survivin and caspase-3expression in the pathogenesis of hepatocellular carcinoma （HCC） . Methods： Forty histologically verified HCC specimens and their neighboring tissues were obtained. Immunohistochemistry was used to detect protein expressions of survivin and caspase-3. TUNEL was employed to examine the apoptosis index of HCC tissues. Results- Survivin protein expression was detected in 34 of 40 （85%） cases. In contrast, no expression of survivin in corresponding noncancerous tissues was detected. The positive rate of survivin expression in the cases with intrahepatic metastasis was 93.5 %, higher than those without intrahepatic metastasis （55.6 %, P 〈 0.05）, and the rate of survivin expression in the cases with portal vein invasion was 92.8%, higher than those without portal vein invasion （66.7%, P〈0.05） . The levels of survivin mRAN in cases with intrahepatic metastasis （1.105±0.396） and portal vein invasion （ 1.137± 0.404） were significantly higher than those without intrahepatic metastasis （0.572 ± 0.082） and portal vein invasion （0.627 ± 0.122, P〈0.05） . The expression of caspase-3 was detected in 15 of 40 （37.5%） cases and 77.5 % in noncancerous tissues. By TUNEL the survivin expression was significantly associated with reduced apoptosis index [ （1.152% ±0.326%） vs. （ 4.502%± 0.830%）, P〈0.05] .In contrast caspase-3 expression was associated with increased apoptosis index （5.016%±0.370% vs 1.927%±0.237%, P〈0.05） .The expression of caspase-3 was 29.4% in the cases with survivin expression lower than the cases without survivin expression （83.3 % ） . Conclusion： Survivin expression may play an important role in HCC carcinogenesis. And the expression of survivin is associated with reduced apoptosis index.