Liu Wen, Wang You, Zhang Chuanling, Huang Baoshan, Bai Jin, Tian Lijun
Clinical Laboratory, The Children's Hospital of Xuzhou Xuzhou, Jiangsu, China.
Department of Obstetrics and Gynecology, RenJi Hospital Shanghai, China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):4001-7. eCollection 2015.
Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of hepatocellular carcinoma (HCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 90 cases HCC tissues and paired adjacent non-cancerous tissues. We analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival using two independent HCC cohorts TMA. Our data showed that Cul1 expression was apparently increased in HCC tissues compared with paired adjacent non-tumor tissues. We also demonstrated that Cul1 staining was significantly correlated with tumor size, histology grade and TNM stage. Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in HCC patients. Finally, univariate and multivariate Cox proportional hazards regression analysis investigated that high Cul1 expression was a strong independent prognostic indicator of HCC. Our data indicated that Cul1 may be an important prognosis marker for human HCC.
Cullin1（Cul1）是泛素E3连接酶Skp1/Cullin1/Rbx1/F-box蛋白复合物的一种支架蛋白，该复合物可使参与细胞周期进程、信号转导和转录的多种蛋白质发生泛素化。为了研究Cul1在肝细胞癌（HCC）发生发展中的作用，我们使用包含90例HCC组织及配对的癌旁非肿瘤组织的组织芯片（TMA），通过免疫组织化学方法评估了Cul1的表达情况。我们利用两个独立的HCC队列TMA分析了Cul1表达与临床病理变量及患者生存率之间的相关性。我们的数据显示，与配对的癌旁非肿瘤组织相比，HCC组织中Cul1的表达明显增加。我们还证实，Cul1染色与肿瘤大小、组织学分级和TNM分期显著相关。此外，我们发现HCC患者中Cul1高表达与较差的5年总生存率和疾病特异性生存率密切相关。最后，单因素和多因素Cox比例风险回归分析表明，Cul1高表达是HCC的一个强有力的独立预后指标。我们的数据表明，Cul1可能是人类HCC的一个重要预后标志物。
