利用GEO数据库分析肝细胞癌组织中着丝粒蛋白F基因的表达及其与预后的相关性

Association between the expression of centromere protein F and prognosis in patients with hepatocellular carcinoma:An analysis using GEO database

目的探讨着丝粒蛋白F(CENPF)基因在肝细胞癌(HCC)患者组织中的表达情况及与临床特征和预后的相关性。方法利用在线工具Oncomine分析CENPF在HCC与正常肝组织的表达情况,从美国国立生物技术信息中心的GEO数据库下载相关芯片数据(GSE14520),收集215例HCC组织的基因表达谱及相关临床数据,将其分为CENPF低表达组(n=107)和CENPF高表达组(n=108)。对样本中的CENPF基因表达数据及其对应的临床信息进行分析。计量资料组间比较采用t检验;计数资料组间比较采用χ~2检验;生存分析采用log-rank(Mantel-Cox)检验;生存资料单因素及多因素分析采用Cox比例风险模型。结果数据集证实HCC组织中CENPF表达水平明显高于正常肝组织(t=12.217,P<0.001)。CENPF基因表达水平与AFP水平、肿瘤大小、TNM分期、转移风险有关系(χ~2值分别为6.463、4.338、7.951、17.331,P值均<0.05)。生存分析显示CENPF高表达患者预后明显差于CENPF低表达组(风险比=1.92,95%可信区间:1.24~2.96,P=0.005)。Cox单因素分析显示,HCC患者预后与AFP水平、肿瘤直径、合并肝硬化、肿瘤分期、转移风险及CENPF表达相关(P值均<0.05);Cox多因素分析显示,合并肝硬化、肿瘤分期及CENPF高表达是HCC患者预后的独立危险因素(P值均<0.05)。结论 CENPF基因高表达可能与HCC进展相关,可作为HCC患者的潜在预后生物标志物。

Objective To investigate the association of the expression of centromere protein F（ CENPF） with clinical features and prognosis in patients with hepatocellular carcinoma（ HCC）. Methods The online tool Oncomine was used to measure the expression of CENPF in HCC tissue and normal liver tissue. Related chip data（ GSE14520） were downloaded from the GEO database of National Center for Biotechnology Information. The gene expression profile and related clinical data of 215 HCC tissue samples were collected,and these samples were divided into low CENPF expression group with 107 samples and high CENPF expression group with 108 samples. The expression of CENPF and related clinical information were analyzed. The t-test was used for comparison of continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the log-rank（ Mantel-Cox） test was used for survival analysis; the Cox proportional hazards model was used for univariate and multivariate analyses of survival data. Results The datasets demonstrated that HCC tissue samples had a significantly higher expression level of CENPF than normal liver tissue samples（ t = 12. 217,P〈0. 001）. The expression level of CENPF was associated with alpha-fetoprotein（ AFP） level,tumor size,TNM stage,and metastasis risk（ χ-2= 6. 463,4. 338,7. 951,and 17. 331,all P〈0. 05）. The survival analysis showed that the patients with high CENPF expression had a significantly poorer prognosis than those with low CENPF expression（ hazard ratio = 1. 92,95% confidence interval： 1. 24-2. 96,P = 0. 005）. The univariate Cox analysis showed that the prognosis of HCC patients was associated with AFP level,tumor diameter,liver cirrhosis,tumor stage,metastasis risk,and CENPF expression（ all P〈0. 05）; the multivariate Cox analysis showed that liver cirrhosis,tumor stage,and high CENPF expression were independent risk factors for the prognosis of HCC patients（ all P〈0. 05）. Conclusion High CENPF expression is associated with the progression of HCC,and CENPF might be used as a potential prognostic biomarker for HCC patients.