摘要
目的探讨昼夜相关转录抑制因子(CIART)在肝癌组织中的表达及其与肝癌患者临床特征和预后间的相关性。方法基于癌症基因组图集(TCGA)数据库与人类蛋白质图集(HPA)数据库,比较CIART在肝癌组织和正常肝组织中mRNA及蛋白水平的表达量;分析CIART mRNA表达量与肝癌患者临床特征及预后间的相关性;利用c Bio Portal在线平台分析CIART基因拷贝数变异及其启动子区DNA甲基化情况;采用基因集富集分析(GSEA)研究CIART基因表达水平与京都基因和基因组百科全书(KEGG)通路基因集的相关性。结果 CIART在肝癌组织中mRNA和蛋白水平表达量均较正常肝组织呈现上调,且CIART mRNA表达量对肝癌具有较好的诊断效能(AUC=0. 7794,P <0. 01)。除患者性别(P <0. 01)外,CIART mRNA表达量与肝癌患者其余临床病理特征间无显著关联(P均> 0. 05)。Kaplan-Meier分析及Cox回归分析提示,CIART mRNA高表达是影响肝癌患者总体生存率和无复发生存率的独立危险因素(P均<0. 05)。370例肝癌患者中有42例(11. 35%)存在CIART基因扩增变异,且与CIART mRNA上调显著相关(P <0. 05)。此外,370例肝癌患者CIART启动子区DNA甲基化程度与CIART mRNA表达量呈显著负相关(Pearson's r=-0. 7126,P <0. 01)。GSEA分析显示,高表达CIART样本中存在基础转录因子(BASAL_TRANSSCRIPTION_FACTORS)通路和碱基切除修复(BASE_EXCISION_REPAIR)通路基因集的富集(P均<0. 05)。结论 CIART可能作为一种癌基因参与肝细胞癌的发生、发展,并具有成为肝细胞癌诊断标志物、预后指标及治疗靶点的潜在价值。
Objective To investigate the expression of circadian associated repressor of transcription( CIART) in hepatocellular carcinoma( HCC) tissues and its association with clinical features and prognosis in HCC patients. Methods Based on the databases of Cancer Genome Atlas( TCGA) and Human Protein Atlas( HPA),the expression levels of CIART mRNA and protein in HCC tissues and normal liver tissues were compared,and the correlation of CIART mRNA expression levels with the clinicopathologic characteristics and prognosis of the patients were analyzed. CIART gene copynumber alterations and DNA methylation in its promoter region were analyzed by c Bio Portal online platform. The correlation between CIART expression level and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway gene set was investigated by gene set enrichment analysis( GSEA). Results The expression levels of CIART mRNA and protein in HCC tissues were up-regulated compared with normal liver tissues,and the expression level of CIART mRNA had better diagnostic efficiency for liver cancer( AUC = 0. 7794,P < 0. 01). Except for patients’ gender( P < 0. 01),there was no significant relationship between CIART mRNA expression level and other clinicopathological features( all P > 0. 05).Kaplan-Meier analysis and Cox regression analysis prompted that CIART mRNA high-expression was the independent risk factor influencing overall survival rate and recurrence-free survival rate of HCC patients( all P < 0. 05). There were amplification variants of CIART gene in 42( 11. 35%) of 370 patients with HCC,and the variants were significantly correlated with up-regulation of CIART mRNA expression( P < 0. 05). In addition,the degree of CIART DNA methylation in its promoter region was significantly negatively correlated with CIART mRNA level in 370 HCC patients( Pearson’s r =-0. 7126,P < 0. 01). GSEA analysis showed that there were gene set enrichments of basal transcription factor( BASAL_TRANSSCRIPTION_FACTORS) pathway and base excision repair( BASE_EXCISION_REPAIR) pathway in
作者
余斌
丁佑铭
廖晓锋
汪斌
陈晓燕
YU Bin;DING You-ming;LIAO Xiao-feng;WANG Bin;CHEN Xiao-yan(Department of Hepatobiliary and Laparoscopic Surgery,Renmin Hospital of Wuhan University,Wuhan,Hubei 430060,China)
出处
《中国临床研究》
CAS
2019年第1期1-7,共7页
Chinese Journal of Clinical Research
关键词
肝细胞癌
癌症基因组图集数据库
昼夜相关转录抑制因子
基因拷贝数变异
DNA甲基化
基因集富集
预后
Hepatocellular carcinoma
Cancer Genome Atlas database
Circadian associated repressor of transcription
Gene copy-number alterations
DNA methylation
Gene set enrichment
Prognosis
