长链非编码RNA ZIM2-AS1在肝细胞癌中的表达及其临床意义

Expression and clinical significance of long non-coding RNA ZIM2-AS1 in hepatocellular carcinoma

目的:利用癌症基因组图谱(TCGA)数据探讨长链非编码RNA(lncRNA)ZIM2-AS1在肝细胞癌(HCC)中的表达及其临床意义和诊断价值。方法:从TCGA数据库下载374例HCC组织样本和50例癌旁组织样本的转录组测序(RNA-seq)数据及相关临床资料,基于R语言进行相关生物信息学分析,以解析ZIM2-AS1在HCC中的表达模式及其与临床病理特征、预后及免疫细胞浸润的相关性,并评估其在HCC中的诊断价值;采用qRT-PCR检测ZIM2-AS1在人正常肝细胞及不同HCC细胞系中的表达情况。结果:ZIM2-AS1在HCC组织中的表达呈升高趋势(P<0.001),其表达水平与患者年龄、性别、肿瘤N分期、组织学分级和AFP水平显著相关(P均<0.05),且高表达患者的总生存期(OS)和疾病相关生存期(DSS)显著短于低表达患者(P<0.05),是影响HCC患者OS的独立危险因素。肿瘤免疫细胞浸润分析显示,ZIM2-AS1与Th2细胞、CD56brightNK细胞、滤泡辅助性T细胞(Tfh)、中性粒细胞和浆细胞样树突状细胞(pDC)的浸润水平显著相关(|Spearman's r|>0.1,P<0.05)。受试者工作特征(ROC)曲线分析显示ZIM2-AS1表达水平对HCC、N0分期、组织学分级G1和G2期、OS及DSS均具有一定诊断价值(AUC均>0.50)。qRT-PCR结果显示ZIM2-AS1在HCC细胞系中的表达水平显著高于人正常肝细胞(P均<0.05)。结论:LncRNA ZIM2-AS1的高表达是HCC预后不良的独立危险因素,具有成为HCC诊断、预后判断及肿瘤免疫微环境评估生物标志物的潜在应用价值。

Objective:To explore the expression of long non-coding RNA(lncRNA)ZIM2-AS1 in hepatocellular carcinoma(HCC)and its clinical significance as well as diagnostic value using the data obtained from the Cancer Genome Atlas(TCGA).Meth⁃ods:The transcriptome sequencing(RNA-seq)data and clinical information of 374 HCC tissues and 50 paired paracancerous tissues were gathered from the TCGA database,then the expression trends of ZIM2-AS1 in HCC and its correlation with clinicopathological features,prognosis,immune cell infiltration,as well as diagnostic value was inspected by bioinformatics analysis using relevant R packages.The expression of ZIM2-AS1 in human normal liver cell line and HCC cell lines was examined by qRT-PCR.Results:The ex-pression of ZIM2-AS1 was highly expressed in HCC tissues(P<0.001),and its expression level was significantly correlated with age,gender,N stage,histologic grade and AFP level(P all<0.05).The overall survival(OS)and disease specific survival(DSS)of patients with high ZIM2-AS1 expression were significantly shorter than those of patients with low expression(P<0.05),and ZIM2-AS1 was an in-dependent risk factor affecting OS.Immune cell infiltration analysis showed that ZIM2-AS1 was closely related to the infiltration of Th2 cells,CD56brightNK cells,follicular helper T cells(Tfh),neutrophils and plasmacytoid dendritic cells(pDC)(|Spearman's r|>0.1,P<0.05)in HCC.ROC curve analysis revealed that the expression level of ZIM2-AS1 possesse potential diagnostic value in HCC,N0 stage,histologic grade G1 and G2,OS and DSS(AUC all>0.50).qRT-PCR results showed that the expression level of ZIM2-AS1 in HCC cell lines was significantly higher than that in human normal liver cells(P all<0.05).Conclusion:The elevated expression of lncRNA ZIM2-AS1 is an independent risk factor for poor prognosis of HCC patient and has potential application value as a biomarker for HCC diagnosis,prognosis as well as tumor immune microenvironment assessment.