HCV C蛋白、p53、Mdm2、p14和p21在原发性肝癌中的表达及相关性

目的:研究原发性肝癌(HCC)组织中核心蛋白、突变p53、Mdm2、p14和p21的表达及其相关性,探讨HCV核心蛋白对突变p53、Mdm2、p14和p21表达影响及临床意义。方法:收集42例HCC石蜡组织,采用免疫组织化学EnVision法检测HCC组织中核心蛋白、突变p53、Mdm2、p14和p21的表达,用统计学方法及临床联系分析它们之间的关系。结果:核心蛋白、突变p53、Mdm2、p14和p21的阳性表达主要定位于细胞核中;HCC组织中核心蛋白、突变p53、Mdm2、p14和p21阳性率分别为40.5%、47.62%、75.57%、45.24%、19.05%;5组间的Kruskal-Wallis检验P=0.000,差异显著,核心蛋白与突变p53、Mdm2、p14和p21间的Mann-WhitneyU秩和检验P值分别为0.043、0.009、1.0、0.023;HCVC蛋白与突变p53、p14、p21阳性强度两者间相关性Spearman检验P值分别为0.000、0.000、0.43,相关系数rs分别为0.67、0.64、-0.29;p53和Mdm2、p21阳性强度间相关性Spearman检验p值为0.000、0.174,rs分别为0.72、-0.45。结论:在HCV感染的HCC中HCVC蛋白可能促进野生p53突变和表达,p14的表达与C蛋白有关联;突变p53和p14很可能促进Mdm2的表达;HCC中p21表达缺陷是十分常见的,HCV相关的HCC主要与p53通路改变有关,C蛋白可能下调p21的表达。因此,HCV相关的HCC中C蛋白、突变p53、Mdm2很可能促进肝细胞增生或恶性生长。

Expression of HCV core, p53, Mdm2, p14ARF and p21WAF1/CIP1 proteins in HCC and their correlation

Objective:To investigate expression of HCV core, mutant p53,Mdm2,p14 ARF p21 WAF1/CIP1proteins and correlation of these proteins in the HCC tissues ; to explore weather HCV core protein affects expression of mutant p53,Mdm2, p14 ARF p21 WAF1/CIP1proteins and their clinic significance. Methods: To collect paraffin-embedded tissues of 42 cases with HCC and determine the expression of HCV core, mutant p53,Mdm2,p14 ARFand p21 WAF1/CIP1 proteins with immunohistochemical method, using EnVision method; analyze the correlation of these proteins by statistic methods. Results: The positive expression of HCV core, mutant p53,Mdm2,p14 ARFp21 WAF1/CIP1 proteins primarily lies in the nucleus; the positive rates of mutant p53, Mdm2, p14 ARF ,protein expression were respectively 40.5%,47.62%,75.57%,45.24%,19.05% in the HCC, and so there was significantly difference(P<0.000) among the five groups of protein expression; p values of correlationship test of positive intensity between HCV core and mutant p53,HCV core and p14 ARFHCV core and p21 WAF1/CIP1expression were respectively0.000,0.000,0.43, while the correlation coefficients were respectively 0.67,0.64,-0.29; p values of correlationship test of positive intensity between mutant p53 and Mdm2,p53 and p21 protein expression were respectively 0.000,0.174, while the correlation coefficients were respectively 0.72,-0.45. Conclusion: HCV core protein probably promotes wild type's transfer to mutant type of p53 and its' expression; HCV core protein together with mutation p53 also probably promotes expression of Mdm2 protein, while the core protein maybe affect the expression of p14 ARFprotein; the high absence of p21 WAF1 protein was very common in HCC, and the HCC related with HCV is correlated with p53 pathway change, with C protein downregulating p21 expression; hence, HCV core protein together with mutation p53,Mdm2 proteins enhances the hepatocytes proliferation and malignance.