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Comprehensive analysis of competitive endogenous RNAs network reveals potential prognostic lncRNAs in gastric cancer

机译:竞争性内源性RNAs网络的全面分析揭示了胃癌的潜在预后性lncRNAs

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摘要

Long non-coding RNAs (lncRNAs) are key regulators of a range of human diseases, including various cancers, with multiple previous studies having explored lncRNA dysregulation in the context of gastric cancer (GC). The present study sought to expand upon these previous results by downloading lncRNA, mRNA, and microRNA (miRNA) expression profiles derived from 180 GC tissues and 24 normal control tissues within the Cancer Genome Atlas (TCGA) database. These datasets were then interrogated to identify GC-related differentially expressed (DE) RNAs (|fold change| ≥ 2, FDR< 0.01), leading to the identification of 1946 DE lncRNAs, 123 DE miRNAs, and 3159 DE mRNAs. These results were then used to generate a putative GC-related competitive endogenous RNA (ceRNA) network composed of 131 lncRNAs, 9 miRNAs, and 78 mRNAs. Subsequent survival analyses based upon this network revealed 17 of these lncRNAs to be significantly associated with GC patient survival ( < 0.05). Further multivariable Cox regression and lasso analyses allowed for the construction of an 8-lncRNA risk score that was able to effectively predict GC patient survival with good discriminative ability. The Kaplan-Meier Plotter database further confirmed that network hub genes that were related to these 8 lncRNAs were associated with GC patient prognosis ( < 0.05). As the ceRNA network in the present study was constructed with a focus on both disease stage and differential gene expression, it represents a key resource that will offer valuable insights into the mechanistic roles of ceRNA pathways in GC development and progression.
机译:长的非编码RNA(lncRNA)是包括多种癌症在内的一系列人类疾病的关键调节因子,之前的多项研究都探索了在胃癌(GC)背景下lncRNA失调。本研究试图通过下载来自癌症基因组图谱(TCGA)数据库中的180个GC组织和24个正常对照组织的lncRNA,mRNA和microRNA(miRNA)表达谱来扩展这些先前的结果。然后,对这些数据集进行查询,以鉴定与GC相关的差异表达(DE)RNA(|倍数变化|≥2,FDR <0.01),从而鉴定出1946个DE lncRNA,123个DE miRNA和3159个DE mRNA。然后将这些结果用于生成推定的与GC相关的竞争性内源RNA(ceRNA)网络,该网络由131个lncRNA,9个miRNA和78个mRNA组成。基于该网络的后续生存分析表明,这些lncRNA中有17个与GC患者生存率显着相关(<0.05)。进一步的多变量Cox回归和套索分析允许构建8-lncRNA风险评分,该评分能够以良好的判别能力有效预测GC患者的生存。 Kaplan-Meier绘图仪数据库进一步证实,与这8个lncRNA相关的网络中心基因与GC患者的预后相关(<0.05)。由于本研究中的ceRNA网络是着重于疾病阶段和差异基因表达的,因此它代表了一种重要资源,它将为ceRNA途径在GC发育和进程中的机械作用提供有价值的见解。

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