四组分竞争内源性RNA网络的分析揭示了胃癌的潜在生物标志物:综合系统生物学和实验研究

Parvaneh Nikpour, Sadra Salehi-Mazandarani
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引用次数: 0

摘要

背景:胃癌是世界范围内常见的致死性癌症。GC发展背后的分子变化还没有被完全理解。因此,我们构建并分析了一个新的四组分竞争内源性RNA (ceRNA)网络,以引入GC中可信的诊断和预后生物标志物。材料和方法:转录组学和环状RNA (circRNA)数据分别从The Cancer Genome Atlas (TCGA)和Gene Expression Omnibus (GEO)数据库中检索。经过批量效应校正、差异表达分析和相互作用预测,建立了包括长链非编码rna (lncRNAs)、环状rna (circRNAs)、微rna (miRNAs)和信使rna (mrna)在内的ceRNA网络。进行了富集分析,并构建了蛋白相互作用(PPI)网络。提取子网络,利用实时定量聚合酶链反应(qRT-PCR)方法检测两个枢纽cerna的表达变化。最后,进行生存分析以确定潜在的预后rna。结果:构建了包含822个节点和1365条边的四组分ceRNA网络。富集分析揭示了重要的信号通路和基因本体,如神经活性配体-受体相互作用和轴突发生。PPI网络显示了ceRNA网络中mrna之间的相互作用。qRT-PCR显示,与对照组织相比,GC中EPHA5和SNAP91 mrna表达下调。生存分析显示8种mrna和1种lncRNA是胃癌的潜在预后生物标志物。结论:已建立的GC中cerna的四组分网络揭示了GC进展的分子和细胞特征,可作为检查和验证潜在诊断和预后生物标志物以及治疗靶点的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of a four-component competing endogenous RNA network reveals potential biomarkers in gastric cancer: An integrated systems biology and experimental investigation
Background: Gastric cancer (GC) is a common and deadly cancer worldwide. Molecular changes underlying the development of GC are not thoroughly understood. Therefore, we constructed and analyzed a novel four-component competing endogenous RNA (ceRNA) network to introduce plausible diagnostic and prognostic biomarkers in GC. Materials and Methods: Transcriptomics and circular RNA (circRNA) data were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. After batch effect correction, differential expression analysis, and interaction prediction, a ceRNA network including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) was established. Enrichment analyses were performed, and a protein–protein interaction (PPI) network was constructed. Furthermore, a subnetwork was extracted, and using the quantitative real-time polymerase chain reaction (qRT-PCR) method, the expression changes of two hub ceRNAs were examined. Finally, survival analysis was performed to identify potential prognostic RNAs. Results: A four-component ceRNA network containing 822 nodes and 1365 edges was constructed. Enrichment analyses unveiled important signaling pathways and gene ontologies such as neuroactive ligand–receptor interaction and axonogenesis. The PPI network showed the interactions among mRNAs of the ceRNA network. qRT-PCR indicated downregulation of EPHA5 and SNAP91 mRNAs in GC compared to control tissues. Survival analyses revealed eight mRNAs and one lncRNA as potential prognostic biomarkers in GC. Conclusion: The established four-component network of ceRNAs in GC reveals a comprehensive view of the molecular and cellular characteristics of GC progression, which can be considered as a basis to examine and validate potential diagnostic and prognostic biomarkers as well as therapeutic targets.
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