Objective: To analyze the expression of centromere protein U (CENPU) in colorectal cancer and its predictive value for long-term prognosis of the patients.
Methods: We retrospectively analyzed the data of 102 patients with colorectal cancer undergoing radical resection in our hospital between January, 2005 and December, 2011. The expression level of CENPU in colorectal cancer tissue was detected immunohistochemically, and its association with clinicopathological characteristics of the patients were analyzed. The patients were divided into low expression group (n=51) and high expression group (n=51) based on the median CENPU expression level for analysis the value of CENPU for predicting long-term prognosis of the patients after radical resection of the tumors. In the in vitro study, we constructed colorectal cancer cell lines with CENPU interference and CENPU overexpression by lentiviral transfection and assessed the changes in the proliferation, migration and invasion of the cells using CCK-8 assay and Transwell assay.
Results: The protein expression level of CENPU was significantly higher in colorectal cancer tissues than in the adjacent tissues (P < 0.05) and was positively correlated with the expressions levels of Ki67 (r=0.569, P < 0.05) and VEGF-C (r=0.629, P < 0.05). CENPU expression level in colorectal cancer tissue was closely related with tumor progression and clinicopathological stage of the tumor (P < 0.05). Kaplan-Meier survival analysis showed that the patients with high CENPU expression had significantly decreased postoperative overall survival (χ2=11.155, P < 0.05); Cox multivariate regression analysis suggested that CENPU expression level was an independent risk factor affecting the overall survival of the patients after radical resection (HR=1.848, P < 0.05). The results of cell experiments demonstrated that high CENPU expression significantly promoted the proliferation, migration and invasion of the tumor cells.
Conclusion: CENPU is highly expressed in colorectal cancer tissues in closely correlation with tumor progression and may serve as a potential biomarker for evaluating the long-term prognosis of colorectal cancer patients.
目的: 分析着丝粒蛋白U（CENPU）在结直肠癌组织中的表达及对远期预后的评估价值。
方法: 2005年1月~2011年12月，纳入我院结直肠癌根治术患者102例，免疫组化分析CENPU在结直肠癌组织中的表达水平；以CENPU相对表达量的中位数为界将患者分为CENPU低表达组（n=51）和CENPU高表达组（n=51），并进一步分析其对术后患者远期预后的评估价值；在体外采用慢病毒转染的方式将结直肠癌细胞株分为正常对照组、CENPU低表达组及CENPU高表达组，并通过CCK-8和Transwell实验分析其对结直肠肿瘤细胞增殖、迁移和侵袭的影响。
结果: 结直肠癌组织中CENPU在蛋白水平上较癌旁组织显著高表达（t=30.45，P < 0.05），且CENPU表达量与Ki67（r=0.569，P < 0.05）及VEGF-C间均呈显著正相关关系（r=0.629，P < 0.05）；结直肠癌组织中CENPU表达水平与患者肿瘤进展及临床病理分期密切相关（P < 0.05）；K-M生存分析显示CENPU高表达组患者术后总生存期（Log-rank χ2=11.155，P < 0.05）显著降低；多因素Cox回归分析显示CENPU表达水平是影响结直肠癌患者术后总生存期的独立危险因素（HR=1.848，P < 0.05）。此外，体外实验显示CENPU可促进结直肠肿瘤细胞的增殖、迁移和侵袭。
结论: CENPU在结直肠癌组织中高表达，且与肿瘤进展密切相关，有望成为评估根治术后结直肠癌患者远期预后的潜在分子标志物。
Keywords: CENPU; clinicopathological parameters; colorectal cancer; risk factor analysis; survival analysis.