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生物信息学分析 microRNA 靶向基因和微阵列鉴定与巴雷特食管相关的基因。

Bioinformatic analyses of microRNA-targeted genes and microarray-identified genes correlated with Barrett's esophagus.

机构信息

a Honghui Hospital , Xi'an Jiaotong University , Xi'an , China.

b Department of Gastroenterology , the Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.

出版信息

Cell Cycle. 2018;17(6):792-800. doi: 10.1080/15384101.2018.1431597.

Abstract

Barrett's esophagus (BE) is defined as a metaplasia condition in the distal esophagus, in which the native squamous epithelium lining is replaced by a columnar epithelium with or without intestinal metaplasia. It is commonly accepted that BE is a precancerous lesion for esophageal adenocarcinoma. The aim of this study was to investigate the aberrant microRNAs (miRNAs) and differentially expressed genes (DEGs) associated with BE based on online microarray datasets. One miRNA and five gene expression profiling datasets were retrieved from the Gene Expression Omnibus Database. Aberrant microRNAs and DEGs were obtained using R/Bioconductor statistical analysis language and software. 23 dysregulated miRNAs and 632 DEGs demonstrating consistent expression tendencies in the five gene microarrays were identified in BE. Moreover, 1962 target genes of aberrant miRNAs were predicted using three bioinformatic tools, namely TargetScan, RNA22-HSA and miRDB. Ultimately, 93 target DEGs were obtained, after which functional annotation was performed on DAVID Bioinformatics Resources. Among Gene Ontology (GO) biological processes, digestive tract development and epithelial cell differentiation have demonstrated significant associations with BE pathogenesis. In addition, analysis of the KEGG pathways has revealed associations with cancer. To enable further study, one miRNA-target DEGs regulatory network was constructed using Cytoscape. 6 target DEGs demonstrated higher-degree distributions in the network, and ROC analysis indicated that FNDC3B may be the best potential biomarker for BE diagnosis. The data presented herein may provide new perspectives for exploring BE pathogenesis and may offer hits with regard to potential biomarkers in BE diagnosis, prediction and therapeutic evaluation.

摘要

巴雷特食管(BE)是指食管远端的一种化生状态,其中固有鳞状上皮被柱状上皮取代,伴有或不伴有肠上皮化生。普遍认为 BE 是食管腺癌的癌前病变。本研究旨在基于在线微阵列数据集,探讨与 BE 相关的异常 microRNAs(miRNAs)和差异表达基因(DEGs)。从基因表达综合数据库中检索了一个 miRNA 和五个基因表达谱数据集。使用 R/Bioconductor 统计分析语言和软件获得异常 microRNAs 和 DEGs。在 BE 中,鉴定出 23 个失调 miRNA 和 5 个基因微阵列中表现出一致表达趋势的 632 个 DEG。此外,使用三个生物信息学工具(TargetScan、RNA22-HSA 和 miRDB)预测了异常 miRNA 的 1962 个靶基因。最终,获得了 93 个靶 DEG,然后在 DAVID 生物信息学资源上进行了功能注释。在基因本体论(GO)生物过程中,消化道发育和上皮细胞分化与 BE 发病机制有显著关联。此外,KEGG 途径分析也与癌症相关。为了进一步研究,使用 Cytoscape 构建了一个 miRNA-靶 DEGs 调控网络。该网络中的 6 个靶 DEG 分布度较高,ROC 分析表明 FNDC3B 可能是 BE 诊断的最佳潜在生物标志物。本文提供的数据可能为探索 BE 发病机制提供新视角,并为 BE 诊断、预测和治疗评估的潜在生物标志物提供新线索。

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