肝细胞癌中磷酸化p27^kip1的表达及意义  

Expression of Phosphorylated p27^(kip1) Protein and Its Significance in Hepatocellular Carcinoma

作　　者：王酉[1] 陈莉[1] 陆牡丹[2] 李鹏[3] 崔晓鹏[3] 沈爱国[2] 

机构地区：[1]南通大学医学院病理解剖学教研室,江苏省南通市226001 [2]南通大学医学院微生物与免疫学教研室,江苏省南通市226001 [3]南通大学附属医院普外科

出　　处：《中国肿瘤临床》2008年第11期636-639,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30300099);江苏省自然科学基金(编号:BK2003035);江苏省南通市社会发展科技基金资助(编号:S2007041)

摘　　要：目的:探讨p27kip1(p27)10号位丝氨酸(S10)和187号位苏氨酸(T187)磷酸化形式的蛋白在肝细胞癌(HCC)组织中的表达及临床病理意义。方法:免疫组化方法检测10例肝血管瘤旁肝组织、76例HCC及癌旁组织中T187、S10磷酸化p27(P-p27T187、P-p27S10)和p27蛋白的表达,Western blot检测两种磷酸化p27和p27在6例HCC及癌旁肝新鲜组织中的表达,并与增殖细胞核抗原(PCNA)的表达相比较。结果:Western blot显示,P-p27T187与P-p27S10在HCC组织中的表达高于对应的癌旁肝组织。免疫组化结果显示HCC中磷酸化p27、PCNA的表达显著高于癌旁组织和血管瘤旁肝组织(P<0.001)。相关性分析表明HCC中两种磷酸化的p27与p27表达呈负相关,而与PCNA表达呈正相关(P<0.001)。P-p27T187和P-p27S10在HCC中的表达强度与肿瘤病理分级,血清AFP值及坏死之间相关(P<0.05),此外,P-p27S10的表达还与转移相关。结论:P-p27T187、P-p27S10在HCC中高表达,与肝癌的恶性进展相关,在临床病理上具有潜在的应用价值。Objective： To investigate the expression of p27^kip1 phosphorylated at the threonine 187 （Thr187） and serine 10 （Serl0） residues （P-p27Thr187, P-p27Ser10） and its significance in hepatocellular carcinoma （HCC）. Methods： We used immunohistochemistry to detect the expression of P-p27Thr187, P-p27Ser10 and total p27 in 10 samples of liver tissue adjacent to hepatic hemangioma and 76 samples of HCC tissue with corresponding adjacent non-tumor tissue. Fresh specimens from 6 cases of HCC and the adjacent liver tissue were also collected for Western blot analysis. The expression of phosphorylated p27 was analyzed and compared with that of proliferative cell nuclear antigen （PCNA）. Results： Western blot analysis showed that phosphorylated p27 protein expression in HCC tissue was higher than that in adjacent non-tumor liver tissues. Immunohistochemistry showed that phosphorylated p27 and PCNA expression were higher in HCC tissues （P〈 0.001）. There was a positive correlation between phosphorylated p27 and PCNA （P〈0.001）. An inverse correlation was found between phosphorylated p27 and total p27 in HCC （P〈0.001）. The expression of phosphorylated p27 was correlated with histological differentiation, serum alpha-fetal protein levels and necrosis （P〈 0.05）. In addition, the expression of P-p27Ser10 was associated with metastasis （P〈0.05）. Conclusion： The expression of phosphorylated p27 was upregulated significantly in HCC compared with non-tumor tissues. Overexpression of phosphorylated p27 may play an important role in the oncogenesis and development of HCC.

关 键 词：肝细胞癌 增殖细胞核抗原 P27 

分 类 号：R735.7[医药卫生—肿瘤]