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假基因DUXAP8在肝癌中的表达及其临床意义
Expression and clinical significance of pseudogene DUXAP8 in liver cancer
文章发布日期:2020年02月17日  来源:  作者:王纯,叶明亮,陈志航,等  点击次数:135次  下载次数:19次

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【摘要】:目的 探讨DUXAP8在肝癌中的表达和临床意义,并探讨可能的作用机制。方法 收集TCGA数据库中截至2019年6月的肝癌表达数据及临床资料,筛选出同时满足在癌组织与癌旁组织差异表达且影响患者预后的lncRNA。分析DUXAP8表达水平与肝癌患者临床病理特征以及预后的相关性。利用GO和KEGG通路富集方法分析与DUXAP8相关的基因生物功能及其可能参与的生物过程。利用STRING数据库和Cytoscape进行蛋白质相互作用分析并筛选关键基因,然后对关键基因的表达量及其预后情况进行分析并进行文献检索分析。肝癌组织和癌旁组织DUXAP8表达比较采用Wilcoxon秩和检验和Wilcoxon符号秩和检验。不同临床病理特征的患者DUXAP8表达水平比较采用Wilcoxon秩和检验。利用Kaplan-Meier法绘制生存曲线并采用log-rank检验进行组间比较;采用Cox回归分析预后影响因素。Pearson相关法分析DUXAP8的相关基因。结果 非配对样品及配对样品肝癌组织和癌旁组织中DUXAP8的表达水平存在显著差异(P值均<0.001),肝癌组织中DUXAP8表达明显升高。在不同年龄、T分期的患者中DUXAP8表达差异显著(P值均<0.05),年龄≥60岁或T分期等级为T3或T4,DUXAP8表达量较高。单因素分析显示,临床分期、T分期、DUXAP8表达量与患者总生存期相关(P值均<0.001),多因素Cox回归分析结果显示,临床分期晚[风险比(HR)=1.648,95%可信区间(95%CI):1.330~2.709,P<0.001]、高DUXAP8表达仍是预后差的独立危险因素(HR=1.849,95%CI:1.262~2.713,P<0.01)。DUXAP8高表达的样本中,富集了与维持肿瘤细胞的增殖和细胞周期等相关的基因。TOP2A、KIF2C、TTK、PLK1、CDCA8、CDC20、NCAPG、BUB1B、BUB1和CCNA2为DUXAP8相关靶基因的Hub基因,主要参与细胞有丝分裂和细胞周期等过程,是肝癌患者预后不良的相关因素(P值均<0.05)。结论 DUXAP8高表达是肝癌患者预后不良的危险因素,DUXAP8可能通过影响细胞增殖、周期等过程促进肝癌的发生发展。
【Abstract】:Objective To investigate the expression, clinical significance, and potential mechanism of action of DUXAP8 in hepatocellular carcinoma. Methods The expression data of liver cancer and related clinical data published up to June 2019 were collected from TCGA database to screen out the differentially expressed long non-coding RNAs (lncRNAs) between liver cancer tissue and adjacent tissue which affected the prognosis of patients. The association of the expression level of DUXAP8 with clinicopathological features and prognosis was analyzed. Gene ontology (GO) and KEGG pathway enrichment analysis was used to investigate the biological functions and biological processes of DUXAP8-related genes. The STRING database and Cytoscape were used to analyze protein-protein interactions and screen out key genes, and then the expression levels of key genes and prognosis were analyzed and a literature search analysis was performed. The Wilcoxon signed-rank test and the Wilcoxon rank-sum test were used to compare the expression of DUXAP8 between liver cancer tissue and adjacent tissue, and the Wilcoxon rank-sum test was used to compare the expression of DUXAP8 between the patients with different clinicopathological features. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for survival comparison between groups; a Cox regression analysis was used to identify the influencing factors for prognosis. A Pearson correlation analysis was used to analyze DUXAP8-related genes. Results As for the matched and unmatched samples, there was a significant difference in the expression of DUXAP8 between liver cancer tissue and adjacent tissue (P<0.001), and the expression of DUXAP8 in liver cancer tissue was significantly higher than that in adjacent tissue. There was a significant difference in the expression of DUXAP8 between the patients with different ages or T stages (P<0.05), and the patients with an age of ≥60 years or a T stage of T3 or T4 tended to have higher expression of DUXAP8. The univariate analysis showed that clinical stage, T stage, and expression of DUXAP8 were associated with patients’ overall survival (all P<0.001), and the multivariate Cox regression analysis showed that an advanced clinical stage (hazard ratio [HR]=1.648, 95% confidence interval [CI]: 1.330-2.709, P<0.001) and high expression of DUXAP8 (HR=1.849, 95%CI: 1.262-2.713, P<0.01) were independent risk factors for poor prognosis. The genes involved in the maintenance of tumor cell proliferation and cell cycle were enriched in the samples with high expression of DUXAP8. TOP2A, KIF2C, TTK, PLK1, CDCA8, CDC20, NCAPG, BUB1B, BUB1, and CCNA2 were the Hub genes of DUXAP8-related genes and were mainly involved in the processes such as cell mitosis and cell cycle, and they were the factors for poor prognosis of patients with liver cancer (all P<0.05). Conclusion The high expression of DUXAP8 is a risk factor for poor prognosis in patients with liver cancer and DUXAP8 may promote the development and progression of liver cancer by affecting the processes of cell proliferation and cell cycle.
【关键字】:癌, 肝细胞; 假基因; DUXAP8
【Key words】:carcinoma, hepatocellular; pseudogene; DUXAP8
【引证本文】:WANG C, YE ML, CHEN ZH, et al. Expression and clinical significance of pseudogene DUXAP8 in liver cancer[J]. J Clin Hepatol, 2020, 36(3): 580-586. (in Chinese)
王纯, 叶明亮, 陈志航, 等. 假基因DUXAP8在肝癌中的表达及其临床意义[J]. 临床肝胆病杂志, 2020, 36(3): 580-586.

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