基于生物信息学的新型三 miRNA 标志物预测食管癌患者的生存。
A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma.
机构信息
Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
出版信息
Biomed Res Int. 2020 Feb 10;2020:5973082. doi: 10.1155/2020/5973082. eCollection 2020.
OBJECTIVE
We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. . We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING).
RESULTS
With cut-off criteria of < 0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan-Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (, , and ) with a high degree of connectivity were selected as hub genes.
CONCLUSIONS
Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.
目的
我们鉴定了食管癌（ESCA）组织与正常食管组织之间差异表达的 microRNAs（DEMs）。然后，我们通过生物信息学分析构建了一个新的三 miRNA 特征，以预测 ESCA 患者的预后。我们结合了来自基因表达综合数据库（GEO）数据库的两个 microarray 分析数据集和来自基因组图谱（TCGA）数据库的 RNA-seq 数据集，以分析 ESCA 中的 DEMs。从 TCGA 数据库中选择了 168 名 ESCA 患者的临床数据来评估 DEMs 的预后作用。使用 TargetScan、miRDB、miRWalk 和 DIANA 网站预测 miRNA 靶基因。使用数据库 for Annotation, Visualization, and Integrated Discovery (David) 进行功能富集分析，并使用 Search Tool for the Retrieval of Interacting Genes database (STRING) 获得蛋白质-蛋白质相互作用（PPI）网络。
结果
根据 < 0.05 和 |log2FC| > 1.0 的截断标准，从 GEO microarray 数据集和 TCGA RNA-seq 计数数据集鉴定出 33 个重叠的 DEMs，包括 27 个上调和 6 个下调的 miRNA。Kaplan-Meier 生存分析表明，三 miRNA 特征（miR-1301-3p、miR-431-5p 和 miR-769-5p）与 ESCA 患者的总生存率显著相关。单变量和多变量 Cox 回归分析的结果表明，三 miRNA 特征是 ESCA 的一个潜在预后因素。此外，基因功能富集分析表明，三个 miRNA 的靶基因参与各种癌症相关途径，包括病毒致癌、叉头框 O（FoxO）、血管内皮生长因子（VEGF）、人类表皮生长因子受体 2（ErbB2）和哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。在 PPI 网络中，选择了三个具有高连通度的靶基因（、和）作为枢纽基因。
结论
我们的结果表明，三 miRNA 特征（miR-1301-3p、miR-431-5p 和 miR-769-5p）是 ESCA 的一种潜在新型预后生物标志物。
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