肝细胞癌中Thr157磷酸化p27^(kip1)的表达和意义  

The Expression and Significant of Phosphorylation of p27^(kip1) at Threonine 157 in the Hepatocellular Carcinoma

作　　者：李鹏[1,2] 陆牡丹[2,3] 王酉[2,3] 崔小鹏[2] 钱海鑫[1] 沈爱国[4] 

机构地区：[1]苏州大学附属第一医院普外科,江苏苏州215006 [2]南通大学附属医院普外科,江苏南通226001 [3]无锡市妇幼保健院病理科,江苏无锡214002 [4]南通大学医学院微生物与免疫学教研室,江苏南通226001

出　　处：《苏州大学学报（医学版）》2010年第4期777-780,899,共5页Suzhou University Journal of Medical Science

基　　金：国家自然科学基金资助项目(30770488);江苏省自然科学基金资助项目(BK2003035)

摘　　要：目的研究肝细胞肝癌(HCC)组织中157号位苏氨酸磷酸化的p27kip1(p-27kip1Thr157)和增殖细胞核抗原(PCNA、Ki67)的表达,探讨其间相互关系及与临床病理的关系,并分析其与临床预后的关系。方法免疫组化方法检测51例HCC及其癌旁组织、10例肝血管瘤旁肝组织中P-p27kip1Thr157和Ki67蛋白的表达。免疫印迹技术检测8例HCC及其癌旁肝新鲜组织中P-p27kip1Thr157和PCNA的表达情况。结果 (1)P-p27kip1Thr157在HCC组织对应的癌旁组织和血管瘤旁肝组织低或缺失表达,PCNA在HCC中显著高表达(P<0.001)。(2)在HCC中,P-p27kip1Thr157的表达强度与肿瘤病理分级明显相关(P<0.05),Ki67的表达强度与HCC的分化程度、有无坏死和AFP值均明显相关(均P<0.05);HCC中P-p27kip1Thr157与Ki67表达成显著正相关(r=0.604,P<0.001)。(3)Kaplan-Meier和多因素COX回归分析,显示P-p27kip1Thr157可作为HCC患者显著的一个独立的预后指标(P<0.05)。结论 P-p27kip1Thr157可能在HCC的发生发展中发挥重要的作用并有一定的预后评估价值。Objective To investigate the expression of phosphorylation of p27Kip1 at threonine 157（P-p27^kip1 Thr157） in the hepatocellular carcinoma（HCC）,and its correlation with proliferating cell nuclear antigen（PCNA and Ki67）,and clinical outcome.Methods Immunohistochemical analysis for p-p27kip1 Thr157 and Ki67 were performed on paraffin embedded tissues in 10 cases of native liver tissue adjacent to hepatic hemangioma and 51 specimens of HCC along with corresponding nontumoral tissue.Fresh specimens from 8 patients with HCC and adjacent liver tissue were also collected for Western blot analysis.Correlation was analyzed among immunohistochemical-assessed levels of P-p27^kip1 Thr157,survival,and major clinical and pathological variables.Results（1） P-p27^kip1 Thr157 expression in HCC was higher than that in nontumoral liver tissue（P 〈0.001）,while Ki67 expression in HCC were lower than that in nontumoral liver tissue.（2） In HCC,P-p27^kip1 Thr157 expression was positively associated with Ki67（P 〈0.001）.P-p27^kip1 Thr157 overexpression was correlated with histological differentiation（P 〈0.05）,and Ki67 expression was correlated with histological differentiation,tumor necrosis and AFP（P〈 0.05）.（3） In both Kaplan-Meier plot and multivariate Cox regression analysis,the positive expression of P-p27^kip1 Thr157 was significantly associated with poor prognosis（P 〈0.05）.Conclusion P-p27^kip1 Thr157 may play an important role in development of HCC and may be a valuable prognostic factor.

关 键 词：肝细胞癌 P27KIP1 预后 

分 类 号：R735.7[医药卫生—肿瘤]