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胃腺癌中异常表达的长链非编码RNA的鉴定

Identification of aberrantly expressed long non-coding RNAs in stomach adenocarcinoma.

作者信息

Gu Jianbin, Li Yong, Fan Liqiao, Zhao Qun, Tan Bibo, Hua Kelei, Wu Guobin

机构信息

Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Hebei, China.

出版信息

Oncotarget. 2017 Jul 25;8(30):49201-49216. doi: 10.18632/oncotarget.17329.

Abstract

AIM

Stomach adenocarcinoma (STAD) is a common malignancy worldwide. This study aimed to identify the aberrantly expressed long non-coding RNAs (lncRNAs) in STAD.

RESULTS

Total of 74 DElncRNAs and 449 DEmRNAs were identified in STAD compared with paired non-tumor tissues. The DElncRNA/DEmRNA co-expression network was constructed, which covered 519 nodes and 2993 edges. The qRT-PCR validation results of DElncRNAs were consistent with our bioinformatics analysis based on RNA-sequencing. The DEmRNAs co-expressed with DElncRNAs were significantly enriched in gastric acid secretion, complement and coagulation cascades, pancreatic secretion, cytokine-cytokine receptor interaction and Jak-STAT signaling pathway. The expression levels of the nine candidate DElncRNAs in TCGA database were compatible with our RNA-sequencing. FEZF1-AS1, HOTAIR and LINC01234 had the potential diagnosis value for STAD.

MATERIALS AND METHODS

The lncRNA and mRNA expression profile of 3 STAD tissues and 3 matched adjacent non-tumor tissues was obtained through high-throughput RNA-sequencing. Differentially expressed lncRNAs/mRNAs (DElncRNAs/DEmRNAs) were identified in STAD. DElncRNA/DEmRNA co-expression network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predict the biological functions of DElncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate the expression levels of DEmRNAs and DElncRNAs. Moreover, the expression of DElncRNAs was validated through The Cancer Genome Atlas (TCGA) database. The diagnosis value of candidate DElncRNAs was accessed by receiver operating characteristic (ROC) analysis.

CONCLUSIONS

Our work might provide useful information for exploring the tumorigenesis mechanism of STAD and pave the road for identification of diagnostic biomarkers in STAD.

摘要

目的

胃腺癌(STAD)是全球常见的恶性肿瘤。本研究旨在鉴定STAD中异常表达的长链非编码RNA(lncRNA)。

结果

与配对的非肿瘤组织相比,在STAD中总共鉴定出74个差异表达的lncRNA(DElncRNA)和449个差异表达的mRNA(DEmRNA)。构建了DElncRNA/DEmRNA共表达网络,该网络涵盖519个节点和2993条边。DElncRNA的qRT-PCR验证结果与我们基于RNA测序的生物信息学分析一致。与DElncRNA共表达的DEmRNA在胃酸分泌、补体和凝血级联、胰腺分泌、细胞因子-细胞因子受体相互作用以及Jak-STAT信号通路中显著富集。TCGA数据库中9个候选DElncRNA的表达水平与我们的RNA测序结果相符。FEZF1-AS1、HOTAIR和LINC01234对STAD具有潜在诊断价值。

材料与方法

通过高通量RNA测序获得3个STAD组织和3个匹配的相邻非肿瘤组织的lncRNA和mRNA表达谱。在STAD中鉴定出差异表达的lncRNA/mRNA(DElncRNA/DEmRNA)。进行DElncRNA/DEmRNA共表达网络构建、基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析以预测DElncRNA的生物学功能。采用定量实时聚合酶链反应(qRT-PCR)验证DEmRNA和DElncRNA的表达水平。此外,通过癌症基因组图谱(TCGA)数据库验证DElncRNA的表达。通过受试者工作特征(ROC)分析评估候选DElncRNA的诊断价值。

结论

我们的工作可能为探索STAD的肿瘤发生机制提供有用信息,并为鉴定STAD的诊断生物标志物铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/5564761/38b92b00ce96/oncotarget-08-49201-g001.jpg

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