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利用生物信息技术分析iASPP与P53靶基因在肝癌中的临床意义 被引量:1

The Effect of iASPP and P53 Downstream Genes in Hepatocellular Carcinoma
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摘要 目的利用生物信息学分析iASPP在肝细胞癌(HCC)中的表达及其与HCC患者预后的相关性,并挖掘iASPP对P53靶基因的调控,进而预测iASPP与其他基因共同调控HCC发生发展的关系。筛选影响HCC预后的分子标志物与潜在靶点。方法通过数据库数据分析肝癌组织和正常肝组织中iASPP表达差异。选取HCC中iASPP的基因表达谱及相关临床和病理资料,根据iASPP的表达水平将HCC患者分为iASPP高表达组和低表达组,运用SPSS进行生存分析及P53靶基因的表达差异分析,进一步分析P53靶基因表达水平对HCC生存的影响。结果对TCGA数据库、Human Protein Atlas数据库和Oncomine数据库的数据分析,结果显示肝癌组织中iASPP基因表达较正常肝组织明显升高(P=0.001)。肝癌患者中,iASPP高表达患者整体生存较低表达患者更差(P<0.05),无病生存期和无进展生存期有差异但不显著。iASPP高表达患者P53代表性靶基因PMAIP1、RAP2B、BBC3、HES2表达水平较低表达患者显著升高;通过对Human Protein Atlas数据库数据研究PMAIP1、RAP2B、BBC3、HES2表达量与HCC的生存关系,发现PMAIP1(P=0.0020)、RAP2B(P=0.00016)、HES2(P=0.00026)影响HCC患者总体生存。结论iASPP在HCC组织中高表达,并影响HCC患者的预后。iASPP高表达可能通过影响P53靶基因PMAIP1、RAP2B、BBC3、HES2的表达水平,进而发挥促肿瘤细胞增殖的作用。iASPP、PMAIP1、RAP2B、HES2表达量与总体生存有关,有望成为判断HCC预后的分子标志物指标。 Objective To study the role of iASPP and the mechanism in hepatocellular carcinoma(HCC),to identify the expression of iASPP and the effect of iASPP levels to prognosis and P53 target genes expression.Methods The expression of iASPP in HCC tissues and normal hepatic tissues from database were analyzed by bioinformatic method,a dataset containing gene expression profile of HCC tissues was collected,as well as the clinical and pathological data of HCC patient.The patient were divided into iASPP higher expression group and iASPP lower expression group according to the median and survival analysis was done.The expression of P53 downstream genes in the 2 groups were analyzed,and determined the effect of these genes to prognosis of patient with HCC.Results iASPP expression was markedly higher in HCC tissues than in normal liver tissues(P=0.001),and patients with higher iASPP expression have significantly worse overall survival(OS)than those with lower iASPP expression(P<0.05).The 2 groups tended to differ in progression-free survival(PFS),but it was not significant(P=0.175).The patients with higher iASPP show significantly higher PMAIP1、RAP2B、BBC3、HES2 expression than that of patients with lower iASPP.More importantly,high PMAIP1(P=0.0020)、RAP2B(P=0.00016)、HES2(P=0.00026)expression were associated with worse survival of HCC.Conclusion iASPP expression was increased in HCC tissues and the patients with higher expression had poor prognosis.High iASPP may regulate P53 target genes PMAIP1,RAP2B,BBC3 and HES2,which in turn affect the HCC cells proliferation and the survival of HCC patient.Survival analysis showed that the expression of iASPP、PMAIP1、RAP2B、HES2 was correlated with overall survival,it could be used as potential biomarkers for prognosis of HCC.
作者 敖枫华 邱杨 熊文敏 姚景亮 涂子为 叶新芊 李国庆 彭世义 AO Fenghua;QIU Yang;XIONG Wenmin(Jiangxi Cancer Hospital,Nanchang,330029)
机构地区 江西省肿瘤医院
出处 《实用癌症杂志》 2021年第12期1930-1934,共5页 The Practical Journal of Cancer
关键词 肝癌 iASPP凋亡刺激蛋白抑制因子 P53靶基因 TCGA Hepatocellular carcinoma iASPP P53 target genes TCGA database
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