极光激酶A在肝细胞癌中的表达及预后意义

The expression and prognostic significance of Aurora Kinase A in hepatocellular carcinoma

目的探索极光激酶A(AURKA)在肝细胞癌(HCC)中表达和对预后的判断作用。方法从癌症基因组图谱(TCGA)数据库下载并提取HCC患者的mRNA表达谱及临床数据。从正常肝组织与全部肿瘤组织、癌旁正常组织与配对肿瘤组织两个方面对TCGA数据库HCC患者的AURKA mRNA表达情况进行分析,然后在人类蛋白质图谱(HPA)数据库中搜索AURKA,分析AURKA在HCC组织和正常肝组织蛋白质水平的表达情况。根据TCGA数据库HCC患者的TNM分期信息,探索AURKA的mRNA在不同分期的表达情况。采用Kaplan-Meier法分析TCGA数据库HCC患者的AURKA高、低表达(以中位数为截断值)与生存期长短是否显著相关。利用Kaplan-Meier Plotter网站公共资源平台中HCC患者的RNA-seq表达谱数据进行外部验证。对TCGA数据库患者的年龄、性别、分化程度、TNM分期、AURKA的mRNA表达进行Cox单因素和多因素分析。结果TCGA数据库中HCC肿瘤组织共有374例,正常肝组织共有50例,其中肿瘤和正常组织来源于同一患者的配对组织共有50对。TCGA数据库中全部HCC肿瘤组织对比正常肝组织和配对癌旁组织,AURKA的mRNA均显著高表达,并且在蛋白质水平亦表达升高,差异具有统计学意义(P<0.05);随着肿瘤TNM分期的升高,AURKA的mRNA表达呈现逐渐上升趋势,差异具有统计学意义(P<0.05);在TCGA数据库HCC队列中,AURKA的mRNA高表达与HCC不良预后相关,并且在Kaplan Meier Plotter数据库得到验证,差异均具有统计学意义(P<0.05);Cox多因素回归分析显示,TNM分期(HR=1.69,95%CI:1.37~2.10)和AURKA的mRNA表达水平(HR=1.03,95%CI:1.01~1.10)是HCC患者的独立预后影响因素。结论AURKA在HCC中显著高表达且与HCC的不良预后相关,是HCC的预后独立影响因素。

Objective To explore the expression of Aurora Kinase A(AURKA)in hepatocellular carcinoma(HCC)and its prognostic value.Methods mRNA expression profiles and clinical data of HCC patients were downloaded from the Cancer Genome Atlas(TCGA)database.Expression of AURKA mRNA in HCC patients of TCGA database from normal liver tissue and all tumor tissues,normal tissues adjacent to cancer and matched tumor tissues were analyzed,and then expression of AURKA to was investigated in HCC tissues and normal liver tissues in the Human Protein Atlas(HPA)database.According to the TNM stage information of HCC patients in TCGA database,expression of AURKA in different stages was analyzed.Kaplan-Meier method was used to analyze whether the high and low expression of AURKA in HCC patients of TCGA database(with the median as the cut-off value)was significantly related to the length of survival.The RNA-seq expression profile data of HCC patients in the public resource platform of the Kaplan-Meier Plotter website was used for external verification.Cox univariate and multivariate analysis were performed on the age,sex,degree of differentiation,TNM stage,and AURKA mRNA expression of TCGA database patients.Results 374 cases of HCC tumor tissues and 50 cases of adjacent normal liver tissues in the TCGA database were included.All HCC tumor tissues in the TCGA database compared with the paired adjacent tissues mRNA level of AURKA was significantly increased,and the protein level was also increased,the difference was statistically significant(P<0.05);With the tumor TNM stage increase of AURKA mRNA expression showed a gradual upward trend,and the difference was statistically significant(P<0.05);in the TCGA database HCC cohort,high expression of AURKA mRNA was associated with poor HCC prognosis,and was obtained in Kaplan Meier Plotter database.The difference was statistically significant(P<0.05);Cox multivariate regression analysis showed that TNM stage(HR=1.69,95%CI:1.37-2.10)and AURKA mRNA expression level(HR=1.03,95%CI:1.01-1.10)are the independent prognostic factors of HCC patients.Conclusions AURKA is highly expressed in HCC,which is associated with the poor prognosis of HCC.AURKA is an independent prognostic factor of HCC.