Skp2与P27^(kip1)在鼻咽癌组织中的表达及意义

Expression and significance of Skp2 and P27^(kip1) protein in nasopharyngeal carcinoma

目的:F-box蛋白家族中的一员Skp2参与细胞周期抑制蛋白P27kip1泛素化降解,研究发现Skp2在乳腺癌、胃癌、前列腺癌等多种恶性肿瘤中表达增加。本研究旨在探讨Skp2与P27kip1在鼻咽癌组织中的表达及与鼻咽癌多项临床病理特征的关系,并探讨两者的相关性。方法:鼻咽癌组39例,慢性鼻咽炎组24例。标本均经石蜡包埋,HE染色确诊。Skp2和P27kip1蛋白的检测采用免疫组化染色(PV-9000二步法)。结果:(1)Skp2在鼻咽癌组织中的阳性表达率为71.79%,明显高于其在慢性鼻咽炎组织中的阳性表达率(41.67%),差异有统计学意义(P<0.05);P27kip1在鼻咽癌组织中的阳性表达率为35.90%,明显低于其在慢性鼻咽炎组织中的阳性表达率(79.17%),差异有统计学意义(P<0.01);(2)Skp2、P27kip1的蛋白表达与鼻咽癌的临床分期、颅神经侵犯有关(P<0.05),与年龄、性别、分化程度、颈淋巴结转移无关(P>0.05);(3)Skp2、P27kip1在鼻咽癌组织中的表达呈负相关(rs=-0.373,P=0.019)。结论:鼻咽癌中Skp2蛋白表达与靶蛋白P27kip1蛋白降解有关,Skp2、P27kip1可能与鼻咽癌的发生发展有关,联合检测Skp2、P27kip1蛋白表达可作为判断鼻咽癌生物学行为的指标之一。

Objective： The F-box protein Skp2 is required for the ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor P27^kip1 . Overexpression of Skp2 has been reported in many cancers including breast carcinoma, gastric carcinoma and prostate cancer. The purpose of this study is to investigate the correlation of Skp2 and P27^kip1 expression with the clinical pathological features of nasopharyngeal carcinoma, and the correlation between expression of Skp2 and P27^kip1 in nasopharyngeal carcinoma. Methods： Thirty-nine eases of nasopharyngeal carcinoma and twenty-four cases of chronic nasopharyngitis were enrolled in this experiment. All specimens were proved by formallin- fixed paraffin-embedded slides with the hematoxylin eosin staining. Expression of Skp2 and P27^kip1 was determined by using an immunohistochemical staining （PV-9000 two-step kit）. Result： The Skp2 labeling frequency （71.79 % ） in nasopharyngeal carcinoma was significantly higher than that （41.67%） in chronic nasopharyngitis（ P 〈 0.05）. The positive rate of P27^kip1 expression in nasopharyngeal carcinoma was 35.90%, which was remarkably lower than that （79.17%） in chronic nasopharyngitis （ P 〈 0.01 ）. Expression of Skp2 and P27^kip1 protein in nasopharyngeal carcinoma was correlated with the clinical stage and cranial nerve encroachment （ P 〈 0.05）, but not correlated with the patient age, sex, histological grade, or lymph node metastases （ P 〉 0.05）. Skp2 expression was inversely correlated with P27^kip1 in nasopha- ryngeal carcinoma（ rs = -0.373, P = 0.019）. Conclusion： Expression of Skp2 protein may decrease the P27^kip1 level in human nasopharyngeal carcinoma, indicating it is involved in the development of human nasopharyngeal carcinoma. Skp2 and P27^kip1 may be used as hopeful markers for predicting the clinical pathological features and the prognosis of these patients.