机构地区:[1]宜昌市第二人民医院,三峡大学第二人民医院消化内科,湖北宜昌443000 [2]宜昌市第二人民医院,三峡大学第二人民医院肿瘤科,湖北宜昌443000
出 处:《临床肝胆病杂志》2020年第5期1087-1090,共4页Journal of Clinical Hepatology
摘 要:目的筛选胆管癌(CCA)中关键基因间长链非编码RNA(lincRNA),并研究其表达与患者预后的关系。方法CCA表达量和临床数据来自于人类癌症基因组图谱(TCGA)。数据集GSE107943 CCA表达数据获取自高通量基因表达数据库(GEO)。利用R软件进行差异性基因分析,确定肿瘤和正常样品之间显著差异性表达的lincRNA;筛选关键lincRNA。使用受试者工作特征曲线(ROC曲线)分析基因表达对CCA的诊断意义。使用Kaplan-Meier生存曲线分析患者预后。基因富集分析分析显著富集分通路。实时荧光定量PCR验证临床样本中基因表达。结果通过筛选得到451个同时在TCGA和GSE107943数据集上调的lincRNA和154个同时两个数据集下调的lincRNA。在TCGA和GSE107943数据集中lincRNA RP11-488L18.10在肿瘤组织中丰度较高。利用TCGA和GSE107943数据集对lincRNA RP11-488L18.10的表达与CCA的关系进行ROC曲线分析,结果显示,TCGA中AUC=1,P<0.0001;在GSE107943中AUC=0.9469,P<0.0001。在TCGA中,lincRNA RP11-488L18.10的高表达可以显著预测CCA的总生存率(P=0.016)和无复发生存率(P=0.017);在GSE107943中,lincRNA RP11-488L18.10的高表达可以显著预测CCA的总生存率(P=0.023)和无复发生存率(P=0.005)。lincRNA RP11-488L18.10与微型染色体维持蛋白2呈显著正相关。相对于癌旁组织,CCA组织中lincRNA RP11-488L18.10(P=0.010)和MCM2(P=0.023)均高表达。结论lincRNA RP11-488L18.10与CCA的发生及预后密切相关,有望成为CCA诊断和治疗的作用靶点。Objective To screen out the key intergenic long non-coding RNAs(lncRNAs)in cholangiocarcinoma(CCA)and their association with patient prognosis.Methods CCA expression and clinical data were obtained from The Cancer Genome Atlas(TCGA).High-throughput gene expression data in GSE107943 dataset were obtained from the Gene Expression Omnibus(GEO).R software was used to analyze differentially expressed genes and determine significantly differentially expressed lncRNAs between tumor and normal samples,and the key lncRNAs were screened out.The receiver operating characteristic(ROC)curve was used to analyze the value of gene expression in the diagnosis of CCA;the Kaplan-Meier survival curves were used to analyze prognosis;Gene Set Enrichment Analysis(GSEA)was used to investigate significantly enriched pathways;quantitative real-time PCR was used to verify gene expression in clinical samples.Results A total of 451 upregulated lncRNAs and 154 downregulated lncRNAs in both TCGA and GSE107943 dataset were screened out.The lncRNA RP11-488L18.10 in TCGA and GSE107943 dataset was highly abundant in tumor tissue.Based on TCGA and GSE107943 dataset,the ROC curve analysis of the association between lncRNA RP11-488L18.10 expression and CCA showed that the expression of lncRNA RP11-488L18.10 had an area under the ROC curve of 1 in TCGA(P<0.0001)and 0.9469 in GSE107943(P<0.0001).In TCGA,the high expression of lncRNA RP11-488L18.10 significantly predicted overall survival rate(P=0.016)and recurrence-free survival rate(P=0.017)in patients with CCA;in GSE107943,the high expression of lncRNA RP11-488L18.10 significantly predicted overall survival rate(P=0.023)and recurrence-free survival rate(P=0.005)in patients with CCA.LncRNA RP11-488L18.10 was significantly positively correlated with MCM2.Compared with the adjacent tissue,CCA tissue had high expression of lncRNA RP11-488L18.10(P=0.010)and MCM2(P=0.023).Conclusion LncRNA RP11-488L18.10 is closely associated with the development and prognosis of CCA and thus may become a target for the di
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