CEP55蛋白在原发性肝细胞癌组织中的表达与临床特征及预后的相关性分析

A Correlation Analysis of the Expression of CEP55 Protein in Primary Hepatocellular Carcinoma Tissues with Clinical Features and Prognosis

目的分析中心体蛋白55(CEP55)在肝细胞癌(HCC)组织中的表达与临床特征及预后的相关性,为揭示肝癌诊断和治疗的新目标和策略提供依据。方法基于TCGA-LIHC数据库分析CEP55在HCC和相应的正常组织中的表达差异,并进一步分析其与生存预后的关系。纳入185例于2015年4月至2016年7月在我院肝胆外科完成了肝切除术的HCC患者,对手术切除的肿瘤组织和癌旁组织(距离肿瘤边缘>5.0cm)制作组织蜡块。采用免疫组织化学染色法检测组织CEP55蛋白表达,分析CEP55表达与HCC患者不同临床特征的关系。采用Kaplan-Meier法绘制生存曲线,并使用Log-rank分析CEP55表达与预后的相关性。采用Logistic回归模型分析影响原发性肝癌患者预后的危险因素。结果基于TCGA-LIHC数据库,418例肝癌组织中CEP55基因拷贝数明显高于癌旁正常组织(P<0.05),且根据每组CEP55表达水平的中位数值将患者分为两组。与LIHC队列中的低表达组相比,CEP55高表达组的总生存期(OS)和无进展生存期(PFS)明显缩短(Log-Rank检验,P<0.05)。CEP55蛋白的表达与患者血管有无浸润、肿瘤直径、BCLC分期、T分期、N分期、分化程度、AFP水平有关(P<0.05)。随访5年,CEP55蛋白高表达组和低表达组患者5年OS分别为64.9%(63/97)、84.0%(74/88)(Log-Rankχ^(2)=10.192,P=0.001);5年PFS分别为54.6%(53/97)、69.3%(61/88)(Log-Rankχ^(2)=5.750,P=0.016)。经单因素和多因素Logistic回归分析,肿瘤组织CEP55高表达是影响患者预后的独立危险因素之一(P<0.05)。结论CEP55蛋白在HCC组织中普遍呈高表达,其与患者预后不良有关,可作为肝癌早期诊断或潜在治疗靶点的分子生物学指标。

Objective To analyze the correlation between the expression of centrosomal protein 55(CEP55)protein in hepatocellular carcinoma(HCC)tissues and clinical features and prognosis,and to provide the reference basis for revealing new targets and strategies for the diagnosis and treatment of hepatocellular carcinoma.Methods Based on the TCGA-LIHC database,we analyzed the expressions of CEP55 in HCC and the corresponding normal tissues,and further analyzed its relationship with survival and prognosis.A total of 185 patients with HCC who underwent hepatectomy from April,2015 to July,2016 in our hospital were included in this study.The paraffin-embedded tissues including the tumor tissues and para-cancerous tissue(less than 5.0 cm from the tumor margin)were prepared.The expression of CEP55 protein was detected by immunohistochemical staining,and the relationship between the expression of CEP55 and the different clinical characteristics of HCC patients was analyzed.Kaplan-Meier method was applied to plot survival curves,and log-rank was performed to analyze the correlation between CEP55 expression and prognosis.Logistic regression model was conducted to analyze the risk factors affecting the prognosis of patients with primary liver cancer.Results Based on the TCGA-LIHC database,the number of copies of CEP55 gene in 418 HCC tissues was significantly higher than that in adjacent normal tissues(P<0.05),and the patients were divided into two groups according to the median value of the expression level of CEP55 in each group.The overall survival(OS)and progression-free survival(PFS)were significantly shorter in the high-expression group of CEP55 than in the low-expression group in the LIHC cohort(Log-Rank Test,P<0.05).The expression of CEP55 protein was correlated with vascular invasion,tumor diameter,BCLC stage,T stage,N stage,degree of differentiation and AFP level(P<0.05).After 5 years of follow-up,the median survival time was 60 months for both the high and low expression group of CEP55,and the OS of the high and low expression group of CEP55 for 5 years were 64.9%(63/97)and 84.0%(74/88)(Log-Rankχ^(2)=10.192,P=0.001),respectively.The 5-year PFS were 54.6%(53/97)and 69.3%(61/88)(Log-Rankχ^(2)=5.750,P=0.016),respectively.Univariate and multivariate logistic regression analysis showed that CEP55 was one of the independent factors affecting the prognosis of patients(P<0.05).Conclusion The high expression level of CEP55 protein in HCC is associated with a poor prognosis,which can be used as a molecular biological indicator for the early diagnosis or potential therapeutic target of HCC.