锌转运蛋白ZIP在肝细胞癌中的表达及其预后意义

Expression of ZIP transporters in human hepatocellular carcinoma and their prognostic significance

目的:通过深入挖掘肿瘤公共数据库中的基因信息,分析ZIP转运蛋白家族成员在肝细胞癌(hepatocellular carcinoma,HCC)中的表达情况及与临床预后的相关性。方法:通过Oncomine和UCSC Xena等肿瘤学公共数据库对ZIP转运蛋白在HCC中的表达情况进行分析;使用cBioPortal数据库探究ZIP家族基因在HCC样本中的遗传改变;利用Kaplan-Meier plotter数据库分析ZIP家族成员表达水平与HCC患者临床预后的关系,探讨其潜在的临床意义。结果:HCC组织中ZIP1、ZIP6和ZIP10 mRNA表达水平明显上调,而ZIP5、ZIP8、ZIP9和ZIP14 mRNA表达水平却明显低于正常组织。进一步分析发现,基因拷贝数改变是引起ZIP1和ZIP14异常表达的重要原因,并且ZIP1扩增的患者的总生存期(OS)显著缩短。Kaplan-Meier分析结果表明,ZIP1、ZIP6和ZIP10高表达的HCC患者,其预后较差,而ZIP2、ZIP11和ZIP12高表达则提示HCC患者预后良好。此外,ZIP表达水平在携带不同类型危险因素的HCC患者预后中具有差异性,例如ZIP4基因高表达可能与肝炎病毒阴性患者的不良预后相关,而ZIP14基因高表达的肝炎病毒阴性或饮酒的HCC患者则预后良好。结论:ZIP转运蛋白表达与肝细胞癌患者临床预后相关,并且具有一定的差异性。

Objective:To explore the expression profiles of members of the ZIP gene familyin hepatocellular carcinoma(HCC)and their correlation with prognosis through in-depth mining of genetic information deposited in public databases.Methods:The Oncomine and UCSC Xena databases were employed to investigate the expression levels of all ZIP genes in HCC.ThecBioPortal tool was used to investigate thegenetic alterations of the HCC samples.The Kaplan-Meier survival analysis was performed to investigate the correlation between ZIP gene expression levels and the survival of HCC patients,aiming to explore their potential clinical significance.Results:Three genes including ZIP1,ZIP6 and ZIP10 displayed obviously elevated mRNA levels,while the expression levels of ZIP5,ZIP8,ZIP9 and ZIP14 mRNA were significantly decreased in HCC tissues compared with normal tissues.Genetic alterations played important roles in the dysregulation of ZIP1 and ZIP14,and patients with genetic alterations of ZIP1 had a shorter overall survival(OS).The Kaplan-Meyer analysis showed that high expressions of ZIP1,ZIP6,ZIP10 indicated worse OS and progression-free survival(PFS)in HCC patients.However,high expressions of ZIP2,ZIP11 and ZIP12 in HCC indicated favorable OS and PFS.In addition,the expression levels of ZIP transporters showed differences in the prognosis of HCC patients with different risk factors.For example,high ZIP4 expression might be associated with poor prognosis in hepatitis virus-negative patients,while high level of ZIP14 predicted the favorable prognosis for HCC patients withhepatitis virus-negative or alcohol consumption.Conclusion:This study revealed that the altered expression levels of ZIP family genes were related to the clinical prognosis of HCC in a different manner.