长链非编码RNA C17orf91在肝细胞癌中低表达的临床意义

Clinical significance of low expression of long non-coding RNA C17orf91 in hepatocellular carcinoma

目的评估长链非编码RNA C17orf91在肝细胞癌患者中的表达水平及其临床意义。方法通过整合全球基因芯片、转录组测序数据鉴定肝细胞癌差异表达基因,计算1381例肝细胞癌及1052例非癌肝组织样本中C17orf91表达水平的标准化平均差(SMD),并合并C17orf91表达水平用于区分肝细胞癌及非癌肝组织的ROC曲线以及AUC。利用癌症基因组图谱分析C17orf91表达水平对肝细胞癌患者预后的影响。为探究C17orf91参与潜在分子通路,本研究从miRecords、DIANA-microTCDS、ElMMo等11个数据库全面搜集C17orf91来源的hsa-miR-22-3p及hsa-miR-22-5p靶基因,将其与肝细胞癌差异表达基因取交集,对基因分子功能展开注释,并据此初步筛选可能具有较高敏感性的抗肝细胞癌药物及其潜在作用靶点。结果肝细胞癌组织中C17orf91表达水平明显下调,其SMD低至-0.96(-1.25~-0.67),对肝细胞癌组织及非癌肝组织具有中等区分能力;且低表达C17orf91预示肝细胞癌患者预后不良。C17orf91来源的hsa-miR-22-3p和hsa-miR-22-5p可能参与抑制细胞迁移正性调控及血管发育;而hsa-miR-22-3p靶基因ADAMTS1可能作为肝细胞癌的治疗靶点。结论低表达C17orf91可能作为肝细胞癌患者预后不良的分子标志物之一。

Objective To evaluate the expression levels and clinical significance of long non-coding RNA(LncRNA C17orf91 in patients with hepatocellular carcinoma(HCC).Methods The data of differentially expressed genes(DEGs)in HCC were obtained from Gene Expression Omnibus(GEO),ArrayExpress,The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx).The SMD of lncRNA C17orf91 expression levels were calculated in 1381 cases of HCC and 1052cases of normal liver tissue samples.The area under the ROC curve(AUC)of C17orf91 expression for distinguishing HCC from normal liver tissues was analyzed.The impact of C17orf91 expression levels on the prognosis of patients with HCC was analyzed based on TCGA.The potential molecular pathways involved in C17orf91 were studied;the target genes of C17orf91-derived hsa-miR-22-3p and hsa-miR-22-5p were screened from 11 databases including miRecords,DIANA-microT-CDS,and EIMMo;the intersections of HCC DEGs with hsa-miR-22-3p and hsa-miR-22-5p targets were obtained to annotate their molecular functions,and screen putative anti-cancer drugs and therapeutic targets for treating HCC.Results LncRNAC17orf91 is significantly down-regulated in HCC tissue samples,and its SMD was-0.96(-1.25,-0.67).The expression of C17orf91 has a moderate ability to distinguish between HCC and normal liver tissue.Low expression of C17orf91 was associated with poor prognosis in HCC patients.C17orf91-derived hsa-miR-22-3p and hsa-miR-22-5p may be involved in inhibiting the positive regulation of cell migration and vascular development.The hsa-miR-22-3p target gene ADAMTS1 may serve as a therapeutic target for HCC.Conclusion Lowly expressed C17orf91 may serve as a molecular markers for poor prognosis in patients with HCC.