Skp2和P27^(kip1)在前列腺癌组织中的表达与临床病理特征的相关性研究

Correlation of Skp2 and P27^(kip1) Protein Expression and Clinicopathological Features of Prostate Cancer

背景及目的:F-box蛋白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和P27kip1在前列腺癌组织中的表达及与前列腺癌各项临床病理特征的关系,并探讨两者的相关性。方法:用免疫组化EnVisionTM方法检测Skp2和P27kip1蛋白在41例前列腺癌和20例良性前列腺增生组织中的表达情况。结果:在前列腺癌中的Skp2蛋白阳性率犤(8.52±2.40)%犦显著高于良性前列腺增生犤(0.21±0.15)%犦(P<0.001)。Skp2蛋白表达与前列腺癌术前血清前列腺特异性抗原(PSA)水平(r=0.360,P=0.021)、局部浸润(r=0.570,P<0.001)、肿瘤分期(r=0.531,P<0.001)、病理分级(r=0.514,P=0.001)呈正相关。在前列腺癌中的P27kip1蛋白阳性率犤(70.71±4.25)%犦显著低于良性前列腺增生犤(97.21±2.10)%犦(P<0.001)。P27kip1蛋白表达与前列腺癌术前PSA水平(r=-0.399,P=0.010)、局部浸润(r=-0.329,P=0.036)、肿瘤分期(r=-0.453,P=0.003)、病理分级(r=-0.290,P=0.046)呈负相关。前列腺癌中P27kip1蛋白与Skp2表达呈负相关(r=-0.572,P<0.001)。结论:前列腺癌中Skp2蛋白表达与靶蛋白P27kip1蛋白降解有关,提示Skp2蛋白可能与前列腺癌的发生发展有关。

BACKGROUND &OBJECTIVE: The F box protein Skp2 is required for the ubiquitin mediated proteolysis of the cyclin depended kinase inhibitor p27kip1. Overexpression of Skp2 has been reported in many cancers, including breast carcinoma, gastric carcinoma, and prostate cancer. The purpose of this study was to investigate the correlation of Skp2 and p27kip1 expression with the clinicopathological features of prostatic carcinoma, and the correlation between expression of Skp2 and p27kip1 in prostate cancer. METHODS: Skp2 and p27kip1 protein expression were evaluated in the tissues of 41 human prostatic carcinomas as well as 20 benign prostatic hyperplasia (BPH) using immunohistochemistry (EnVisionTM method). RESULTS: The Skp2 labeling frequency in prostatic carcinoma (8.52%±2.40%) was significantly higher than that in BPH (0.21%±0.15%)(P< 0.001). The Skp2 protein expression in prostatic carcinoma was positively correlated with preoperative serum prostate specific antigen level (r=0 360,P=0.021), extraprostatic extension (r=0 570,P< 0.001), tumor stage (r=0 531,P< 0.001), and histological grade (r=0 514,P=0.001). The p27kip1 labeling frequency in prostatic carcinoma(70.71%±4.25%)was significantly lower than that in BPH (97.21%±2.10%)(P< 0.001). The p27kip1 protein expression in prostatic carcinoma was inversely correlated with preoperative serum prostate specific antigen level (r=-0 399,P=0.010), extraprostatic extension (r=-0 329,P=0.036), tumor stage (r=-0 453,P=0.003), and histological grade (r=-0 290,P=0.046). Skp2 expression was inversely correlated with p27kip1 in prostate cancer (rho=-0.572,P< 0.001). CONCLUSION: Expression of Skp2 protein may lead to decrease p27kip1 level in human prostatic carcinoma, indicating its involvement in the development of human prostatic carcinoma. It may provide new targets for the therapy of prostate cancer.