p16、p21基因表达缺失在原发性肝癌中的临床意义

The expression and correlation of p16,p21 gene in primary hepatocellular carcinoma

背景与目的:P16,P21蛋白是调控细胞周期的抑制蛋白,在调节细胞增殖中起非常重要的作用,其基因缺失,失活与多种肿瘤的发生,发展有关,本研究观察原发性肝癌中P16、P21蛋白表达及其基因缺失情况,探讨p16、p21基因表达缺失的临床意义。方法:采用回顾性分析方法,收集原发性肝癌42例,正常肝组织(距离癌组织≥2cm)36例,应用Western印迹试验、逆转录聚合酶链式反应(RT-PCR)检测肝癌和正常肝组织中P16、P21蛋白的表达和相应mRNA扩增情况。结果:在癌组织中,P16蛋白缺失率为24例(24/42,57.1%),正常肝组织中P16蛋白缺失率为13.9%(5/36);而相应组织中P21蛋白缺失率分别为45.2%(19/42)和19.4%(7/36)。两者在癌和正常肝组织中缺失差异均有显著性(P<0.05)。14例癌组织(38.9%,14/36)仅p16mRNA转录而未表达蛋白。P16、P21蛋白的低表达与肝癌大小、分化程度关系密切(P<0.05),而与是否有包膜、是否肝硬化等无关。结论:P16、P21蛋白的表达缺失与肝癌发生发展密切相关,两者可作为判断肝癌恶性程度的参考指标。

Background and purpose： P16 and P21 protein are suppressors that are mainly involved in modulating cell cycle and regulating cell proliferation. The deletion, inactivation of p16 and p21 genes may be related to multiple carcinogenesis and progression. This study was to investigate the P16, P21 protein expression, its deletion in hepatocellular carcinoma （HCC） and to evaluate the relationship between the p16, p21 gene and the hepatocarcinogenesis.. Methods： The expression of P16, P21 protein and the gene status in 42 cases of HCC and 36 cases of tumor-adjacent non-cancerous tissues were examined by Western Blotting and Reverse Transcription-Polymerase chain Reaction（RT-PCR）. Results： The loss of p 16 protein expression was observed in 24 cases of HCC （57.1%, 24/42） and in 5 cases of tumor-adjacent non-cancerous tissues （13.9%, 5/36）, there were similar patterns for the loss of P21 protein expression, 45.2% （19/42） in HCC and 19.4% （7/36） in tumor-adjacent non-cancerous tissues, respectively （P〈0.05）. 14 cases（38.9%,14/36） in HCCs only expressed the pl6mRNA but did not express the protein. A lack of p16, p21 expression correlated with histological differentiation grade （P〈0.05） and the tumor size （P〈0.05）, but not with the encapsulation and hepatocirrhosis. Conclusions： The p16 and p21 gene inactivation has a close relationship with hepatocarcinogenesis. P16 and P21 protein may have reference value to estimate the degree of differentiation and prognosis of primary hepatocellular carcinoma.