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感染与未感染胃癌中异常表达的ceRNA网络的综合分析

Comprehensive Analysis of Aberrantly Expressed ceRNA network in gastric cancer with and without infection.

作者信息

Chu Aining, Liu Jingwei, Yuan Yuan, Gong Yuehua

机构信息

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, China.

Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang 110001, China.

出版信息

J Cancer. 2019 Jan 29;10(4):853-863. doi: 10.7150/jca.27803. eCollection 2019.

Abstract

: This study mainly focused on revealing ceRNA network in gastric cancer (GC) with infection after comparing with GC without infection and exploring the biological function and prognostic relevance of related molecules. : The RNA expression profile data of GC patients with or without infection were extracted from TCGA GDC data portal, including 20 GC cases with infection and 168 GC cases without infection. Differentially expressed lncRNAs, miRNAs and mRNAs were unveiled by package edgeR of R, and lncRNA-miRNA-mRNA ceRNA network was constructed by integrating the miRNA target information and the expression data of lncRNAs, miRNAs and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of aberrantly expressed mRNAs were performed to identify the related biological functions and pathologic pathways, and protein-protein interaction (PPI) network was constructed by STRING database. The overall survival (OS) of aberrantly expression lncRNAs and miRNAs were analyzed by package survival of R. A total of 30 gastric cancer tissues were used to validate the bioinformatics analysis results by real-time PCR. : Among the 32 differentially expressed miRNAs, 27 differentially expressed lncRNAs and 257 differentially expressed mRNAs were identified by comparing GC patients with and without infection. Totally 10 miRNA, 11 lncRNA, 219 mRNA were included to build ceRNA network. GO and KEGG analysis revealed that differentially expressed mRNAs involved in the ceRNA network were mainly involved in extracellular exosomes, structural molecular activities, proteolysis and P13K-Akt signaling pathways. And PPI analysis obtained six hub genes of NTS, APOC3, OTX2, KRT13, CALCA, GNG4. Survival analysis showed that four lncRNAs (LINC01254, LINC01287, LINC01524, U95743.1) and four miRNAs (miR-302a, miR-302b, miR-1286, miR-378g) were associated with overall survival of GC with infection. The real-time PCR results showed that, the levels of LINCO1254, LINCO1287, LINCO1524, U95743.1 were significantly higher in positive GC patients than negative patients (=0.02, 0.048, 0.04, 0.036, respectively). : Using TCGA database for data mining, we have successfully constructed a ceRNA regulatory network of GC with infection, consisting of 10 lncRNAs, 11 miRNAs and 219 mRNAs. These findings might provide critical clues for the regulatory role of ceRNA network in the development of GC with infection.

摘要

本研究主要通过与未感染的胃癌(GC)进行比较,聚焦于揭示感染后胃癌中的ceRNA网络,并探索相关分子的生物学功能和预后相关性。从TCGA GDC数据门户提取感染或未感染的GC患者的RNA表达谱数据,包括20例感染的GC病例和168例未感染的GC病例。通过R语言的edgeR软件包揭示差异表达的lncRNAs、miRNAs和mRNAs,并通过整合miRNA靶标信息以及lncRNAs、miRNAs和mRNAs的表达数据构建lncRNA-miRNA-mRNA ceRNA网络。对异常表达的mRNAs进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,以识别相关的生物学功能和病理通路,并通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络。通过R语言的survival软件包分析异常表达的lncRNAs和miRNAs的总生存期(OS)。总共使用30个胃癌组织通过实时PCR验证生物信息学分析结果。通过比较感染和未感染的GC患者,鉴定出32个差异表达的miRNAs、27个差异表达的lncRNAs和257个差异表达的mRNAs。总共纳入10个miRNA、11个lncRNA、219个mRNA构建ceRNA网络。GO和KEGG分析表明,ceRNA网络中差异表达的mRNAs主要参与细胞外囊泡、结构分子活性、蛋白水解和P13K-Akt信号通路。PPI分析获得NTS、APOC3、OTX2、KRT13、CALCA、GNG4这六个枢纽基因。生存分析表明,四个lncRNAs(LINC01254、LINC01287、LINC01524、U95743.1)和四个miRNAs(miR-302a、miR-302b、miR-1286、miR-378g)与感染的GC的总生存期相关。实时PCR结果表明,感染阳性的GC患者中LINCO1254、LINCO1287、LINCO1524、U95743.1的水平显著高于感染阴性患者(分别为=0.02、0.048、0.04、0.036)。利用TCGA数据库进行数据挖掘,我们成功构建了感染后GC的ceRNA调控网络,该网络由10个lncRNAs、11个miRNAs和219个mRNAs组成。这些发现可能为ceRNA网络在感染后GC发展中的调控作用提供关键线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/391d/6400797/404dabf8467f/jcav10p0853g001.jpg

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