Low lncRNA ZNF385D-AS2 expression and its prognostic significance in liver cancer
Low lncRNA ZNF385D-AS2 expression and its prognostic significance in liver cancer
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lncRNA ZNF385D-AS2低表达及其在肝癌中的预后意义
DOI：
10.3892/or.2019.7238
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发表时间：
2019-09-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Fangfang
中科院分区：
文献类型：
--
作者：
Zhang, Ze;Wang, Shouqian;Chen, Fangfang
肝细胞癌（HCC）是一种常见的消化系统疾病，目前尚无有效的治疗方法.锌指蛋白385 D反义RNA 2（ZNF 385 D-AS 2）是一种长链非编码RNA（lncRNA），被预测在人类疾病中发挥作用，包括几种类型的癌症。然而，它还没有被调查与肝癌。因此，本研究旨在阐明lncRNA ZNF 385 D-AS 2在HCC中的预后意义。利用癌症基因组测序-肝细胞肝癌（TCGA-LIHC）数据集分析lncRNA ZNF 385 D-AS 2在肝癌中的表达。采用卡方检验分析临床特征与lncRNA ZNF 385 D-AS 2表达的相关性。采用Kaplan-Meier曲线和考克斯分析评价lncRNA ZNF 385 D-AS 2在患者预后中的意义。同时，进行基因集富集分析（GSEA）以分析最密切相关的细胞学行为。最后，我们使用数据库注释，可视化和集成发现（大卫）和KOBAS软件和基因表达综合数据库（GEO）的数据来分析肝癌中可能的竞争内源性RNA（ceRNA）网络模式以及共表达网络。基于结果，对303例原发性肿瘤患者的RNA-Seq基因表达数据的分析显示，ZNF 385 D-AS 2在肝癌中的表达较低。ZNF 385 D-AS 2的低表达与性别（P=0.050）、T分期（P=0.049）、M分期（P =0.040）、N分期（P<0.001）和临床分期（P=0.037）有关。与ZNF 385 D-AS 2高表达肝癌患者相比，ZNF 385 D-AS 2低表达肝癌患者的中位总生存期较短（P=0.0079）。考克斯分析确定ZNF 385 D-AS 2低表达是肝癌患者总生存期的独立预后变量（AUC=0.594）。共表达和ceRNA预测分析数据提示ZNF 385 D-AS 2与miR-96和miR-182之间可能存在调控信号轴。总之，我们的研究结果表明，ZNF 385 D-AS 2的低表达是肝癌患者预后不良的预测。
Hepatocellular carcinoma (HCC) is a common digestive system disease with no curative treatment. Zinc finger protein 385D antisense RNA 2 (ZNF385D-AS2) is a long non-coding RNA (lncRNA) that has been predicted to function in human diseases, including several types of cancer. Yet, it has not been investigated in relation to liver cancer. Thus, the present study was designed with an aim to elucidate the prognostic significance of lncRNA ZNF385D-AS2 in HCC. The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) collection of data was utilized to analyze the expression of lncRNA ZNF385D-AS2 in liver cancer. Then Chi-square tests were used to evaluate the correlation between clinical characteristics and lncRNA ZNF385D-AS2 expression. The significance of lncRNA ZNF385D-AS2 in patient prognosis was evaluated using Kaplan-Meier curves and Cox analysis. Concomitantly, Gene Set Enrichment Analysis (GSEA) was performed to analyze the most closely related cytological behavior. Finally, we used the Database for Annotation, Visualization and Integrated Discovery (DAVID) and KOBAS software and data from the Gene Expression Omnibus (GEO) database to analyze the possible competing endogenous RNA (ceRNA) network pattern as well as the co-expression network in liver cancer. Based on the results, analysis of RNA-Seq gene expression data for 303 patients with primary tumors revealed low expression of ZNF385D-AS2 in liver cancer. Low expression of ZNF385D-AS2 was found to be significantly associated with sex (P=0.050), T stage (P=0.049), M stage (P=0.040), N stage (P<0.001) and clinical stage (P=0.037). Patients with ZNF385D-AS2 low-expression liver cancers had a shorter median overall survival compared with the patients with ZNF385D-AS2 high-expression liver cancers (P=0.0079). Cox analysis identified ZNF385D-AS2 low-expression as an independent prognostic variable (AUC=0.594) for overall survival in liver cancer patients. Co-expression and ceRNA predictive analysis data suggested that there may be a regulatory signaling axis between ZNF385D-AS2 and miR-96 and miR-182. In conclusion, our results suggests that low expression of ZNF385D-AS2 is predictive of a poor prognosis of liver cancer patients.