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胃腺癌中潜在竞争性内源性RNA(ceRNA)网络的鉴定

Identification of a potential competing endogenous RNA (ceRNA) network in gastric adenocarcinoma.

作者信息

Wu Chen, Hou Xinfang, Li Shuai, Wang Jufeng, Luo Suxia

机构信息

Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

出版信息

J Gastrointest Oncol. 2023 Apr 29;14(2):1019-1036. doi: 10.21037/jgo-22-1201. Epub 2023 Jan 5.

Abstract

BACKGROUND

Recently, a growing body of evidence has revealed the role of competing endogenous RNA (ceRNA) networks in various human cancers. However, there is still a lack of research on the systemic ceRNA network related to gastric adenocarcinoma.

METHODS

The intersection of differentially expressed genes (DEGs) was obtained by mining the GSE54129, GSE13861, and GSE118916 datasets from the Gene Expression Omnibus (GEO) website. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for the enrichment analysis. A protein-protein interaction (PPI) network was established with the STRING online database, and hub genes were identified by Cytoscape software. The prediction of key microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) was conducted by miRNet. The prognostic analysis, expression difference, and correlation analysis of messenger RNAs (mRNAs), lncRNAs, and miRNAs were carried out using the Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, and Encyclopedia of RNA Interactomes (ENCORI).

RESULTS

We identified180 significant DEGs. Extracellular matrix (ECM) receptor interaction, focal adhesion, ECM tissue, and collagen catabolic processes were the most significant pathways in the functional enrichment analysis. Nineteen upregulated hub genes and one downregulated hub gene were found to be significantly associated with the prognosis of gastric adenocarcinoma. Of the 18 miRNAs targeting 12 key genes, only six were associated with a promising prognosis in gastric adenocarcinoma. By comprehensive differential expression and survival analysis, 40 key lncRNAs were identified. Finally, we constructed a network of 24 ceRNAs associated with gastric adenocarcinoma.

CONCLUSIONS

Potential mRNA-miRNA-lncRNA subnets were constructed, each RNA of which can be used as a prognostic biomarker for gastric adenocarcinoma.

摘要

背景

最近,越来越多的证据揭示了竞争性内源性RNA(ceRNA)网络在各种人类癌症中的作用。然而,关于胃腺癌相关的系统性ceRNA网络的研究仍然缺乏。

方法

通过挖掘基因表达综合数据库(GEO)网站上的GSE54129、GSE13861和GSE118916数据集,获得差异表达基因(DEG)的交集。使用注释、可视化和综合发现数据库(DAVID)进行富集分析。利用STRING在线数据库建立蛋白质-蛋白质相互作用(PPI)网络,并通过Cytoscape软件识别枢纽基因。通过miRNet对关键微小RNA(miRNA)和长链非编码RNA(lncRNA)进行预测。使用基因表达谱交互式分析(GEPIA)、Kaplan-Meier绘图仪和RNA相互作用组百科全书(ENCORI)对信使RNA(mRNA)、lncRNA和miRNA进行预后分析、表达差异分析和相关性分析。

结果

我们鉴定出180个显著的DEG。细胞外基质(ECM)受体相互作用、粘着斑、ECM组织和胶原蛋白分解代谢过程是功能富集分析中最显著的途径。发现19个上调的枢纽基因和1个下调的枢纽基因与胃腺癌的预后显著相关。在靶向12个关键基因的18个miRNA中,只有6个与胃腺癌有良好的预后相关。通过综合差异表达和生存分析,鉴定出40个关键lncRNA。最后,我们构建了一个与胃腺癌相关的24个ceRNA网络。

结论

构建了潜在的mRNA-miRNA-lncRNA子网,其中每种RNA都可作为胃腺癌的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e12/10186539/2011d1852588/jgo-14-02-1019-f1.jpg

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