周期素依赖性激酶5激活结合蛋白3在结肠癌组织中的表达及临床意义

Expression and clinical significance of cyclin dependent kinase 5 regulatory subunit associated protein 3 in colon cancer

目的探讨周期素依赖性激酶5激活结合蛋白3(CDK5RAP3)在结肠癌组织中的表达,并分析其表达水平与结肠癌患者临床病理特征及预后的关系。方法通过GEPIA数据库分析CDK5RAP3在肿瘤组织及正常组织中的表达水平;采用组织芯片技术和免疫组织化学染色法,检测88例结肠癌组织以及对应正常组织中CDK5RAP3的表达水平,并分析CDK5RAP3表达水平与结肠癌临床病理特征及预后的关系。采用Cox比例风险回归模型分析影响结肠癌患者预后的独立因素。结果GEPIA数据库分析显示,CDK5RAP3在结肠癌组织中呈低表达,而在正常组织中呈高表达,差异有统计学意义(P<0.05)。同时免疫组化结果也显示,CDK5RAP3在结肠癌组织中以不表达和低表达为主,而在正常组织中以高表达为主。结肠癌癌和正常组织中CDK5RAP3的H-score中位数及四分位数分别为220(205,250)和270(240,290),CDK5RAP3在结肠癌组织中的表达显著低于正常组织,差异有统计学意义(P<0.001)。CDK5RAP3的表达水平与结肠癌各临床病理特征均无关(P>0.05)。Kaplan-Meier生存分析显示,CDK5RAP3低表达的结肠癌患者中位总生存期(OS)为42.6个月,较CDK5RAP3高表达患者显著缩短,差异有统计学意义(P=0.004)。Cox多因素分析结果显示,CDK5RAP3表达水平(HR=0.420,95%CI:0.210~0.839,P=0.014)、脉管侵犯(HR=2.926,95%CI:1.015~8.429,P=0.047)和TNM分期(HR=3.255,95%CI:1.453~7.291,P=0.004)均为影响结肠癌患者预后的独立因素。结论CDK5RAP3在结肠癌组织中的表达下调,有望成为结肠癌患者的预后预测指标。

Objective To investigate the expression of cyclin dependent kinase 5 regulatory subunit associated protein 3(CDK5RAP3)in human colon cancer tissue and its correlation with patients clinicopathological characteristics and prognosis.Methods The CDK5RAP3 expression level between human cancer tissues and adjacent normal tissues according to TCGA data from GEPIA database was compared.The tissue microarray and immunohistochemistry were used to examine the protein expression level of CDK5RAP3 in 88 cases of colon cancer and their adjacent normal tissues.The relationship between the protein expression level of CDK5RAP3 in colon cancer and clinicopathological characteristics and prognosis.Cox proportional hazards regression model was used to analyze the independent factors influencing the prognosis of patients with colon cancer.Results GEPIA online analysis showed that the CDK5RAP3 level of colon cancer tissues was lower than that of normal tissue(P<0.05).Moreover,our immunohistochemistry study showed that the expression of CDK5RAP3 in colon cancer tissues was mainly non-expression and low expression,while it was mainly high expression in normal tissues.The median and quartile of H-score in colon cancer tissues and normal tissues were 220(205,250)and 270(240,290),respectively,and the expression of CDK5RAP3 in colon cancer tissues was significantly lower than that in normal tissues(P<0.001).There was no significant correlation between CDK5RAP3 protein expression and the clinicopathological characteristics of patients with colon cancer(P>0.05).Kaplan Meier survival analysis showed that the median overall survival(OS)of colon cancer patients with CDK5RAP3 low expression level was 42.6 months,which was significantly shorter than that of patients with CDK5RAP3 high expression(P=0.004).Cox multivariate model analysis indicated that the expression level of CDK5RAP3(HR=0.420,95%CI:0.210-0.839,P=0.014),vascular invasion(HR=2.926,95%CI:1.015-8.429,P=0.047)and TNM stage(HR=3.255,95%CI:1.453-7.291,P=0.004)were independent prognostic factors of colon cancer.Conclusion CDK5RAP3 is expressed lowly in colon cancer and can be used as a major factor in the prognosis evaluation of colon cancer patients.