Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Hepatobiliary‑Pancreatic Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Rep. 2019 Sep;42(3):1110-1124. doi: 10.3892/or.2019.7238. Epub 2019 Jul 16.
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.
肝细胞癌 (HCC) 是一种常见的消化系统疾病,目前尚无治愈方法。锌指蛋白 385D 反义 RNA 2 (ZNF385D-AS2) 是一种长链非编码 RNA (lncRNA),据预测在包括多种癌症在内的人类疾病中发挥作用,但尚未在肝癌中进行研究。因此,本研究旨在阐明 lncRNA ZNF385D-AS2 在 HCC 中的预后意义。本研究利用癌症基因组图谱-肝肝细胞癌 (TCGA-LIHC) 数据集分析了肝癌中 lncRNA ZNF385D-AS2 的表达。然后,采用卡方检验评估临床特征与 lncRNA ZNF385D-AS2 表达的相关性。采用 Kaplan-Meier 曲线和 Cox 分析评估 lncRNA ZNF385D-AS2 对患者预后的意义。同时,采用基因集富集分析 (GSEA) 分析与细胞行为最密切相关的分析。最后,我们使用数据库注释、可视化和综合发现 (DAVID) 和 KOBAS 软件以及基因表达综合数据库 (GEO) 数据库中的数据,分析肝癌中可能存在的竞争性内源 RNA (ceRNA) 网络模式以及共表达网络。基于这些结果,对 303 例原发性肿瘤患者的 RNA-Seq 基因表达数据进行分析显示,ZNF385D-AS2 在肝癌中表达水平较低。ZNF385D-AS2 低表达与性别显著相关 (P=0.050)、T 期 (P=0.049)、M 期 (P=0.040)、N 期 (P<0.001) 和临床分期 (P=0.037)。ZNF385D-AS2 低表达肝癌患者的中位总生存期短于 ZNF385D-AS2 高表达肝癌患者 (P=0.0079)。Cox 分析表明,ZNF385D-AS2 低表达是肝癌患者总生存的独立预后变量 (AUC=0.594)。共表达和 ceRNA 预测分析数据表明,ZNF385D-AS2 与 miR-96 和 miR-182 之间可能存在调控信号轴。综上所述,本研究结果表明 ZNF385D-AS2 低表达可预测肝癌患者预后不良。