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Prediction of a competing endogenous RNA co‐expression network as a prognostic marker in glioblastoma

机译:将竞争内源性RNA共表达网络预测为胶质母细胞瘤中的预后标志物

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摘要

Due to its high proliferation capacity and rapid intracranial spread, glioblastoma (GBM) has become one of the least curable malignant cancers. Recently, the competing endogenous RNAs (ceRNAs) hypothesis has become a focus in the researches of molecular biological mechanisms of cancer occurrence and progression. However, there is a lack of correlation studies on GBM, as well as a lack of comprehensive analyses of GBM molecular mechanisms based on high‐throughput sequencing and large‐scale sample sizes. We obtained RNA‐seq data from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) databases. Further, differentially expressed mRNAs were identified from normal brain tissue and GBM tissue. The similarities between the mRNA modules with clinical traits were subjected to weighted correlation network analysis (WGCNA). With the mRNAs from clinical‐related modules, a survival model was constructed by univariate and multivariate Cox proportional hazard regression analyses. Thereafter, we carried out Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, we predicted interactions between lncRNAs, miRNAs and mRNAs by TargetScan, miRDB, miRTarBase and starBase. We identified 2 lncRNAs (NORAD, XIST), 5 miRNAs (hsa‐miR‐3613, hsa‐miR‐371, hsa‐miR‐373, hsa‐miR‐32, hsa‐miR‐92) and 2 mRNAs (LYZ, PIK3AP1) for the construction of a ceRNA network, which might act as a prognostic biomarker of GBM. Combined with previous studies and our enrichment analysis results, we hypothesized that this ceRNA network affects immune activities and tumour microenvironment variations. Our research provides novel aspects to study GBM development and treatment.
机译:由于其高增殖能力和快速的颅内传播,胶质母细胞瘤(GBM)已成为最不可溶解的恶性癌症之一。最近,竞争内源性RNA(Cernas)假设已成为癌症发生和进展的分子生物学机制研究的重点。然而,基于高通量测序和大规模样本尺寸,缺乏对GBM的相关性研究,以及缺乏对GBM分子机制的综合分析。我们从癌症基因组Atlas(TCGA)和基因型 - 组织表达(GTEX)数据库中获得了RNA-SEQ数据。此外,从正常脑组织和GBM组织中鉴定差异表达的MRNA。具有临床性状的mRNA模块之间的相似性进行加权相关网络分析(WGCNA)。利用来自临床相关模块的MRNA,通过单变量和多变量COX比例危害回归分析构建生存模型。此后,我们进行基因本体(GO)和基因和基因组的京都百科全书(Kegg)富集分析。最后,我们通过TargetScan,MirdB,Mirtarbase和Starbase预测LNCRNA,MiRNA和MRNA之间的相互作用。我们确定了2个LNCRNA(Norad,XIST),5 miRNA(HSA-MIR-3613,HSA-MIR-371,HSA-MIR-373,HSA-MIR-32,HSA-MIR-92)和2 MRNA(Lyz,Pik3ap1 )为了建造Cerna网络,这可能是GBM的预后生物标志物。结合以前的研究和我们的浓缩分析结果,我们假设这种Cerna网络影响免疫活性和肿瘤微环境变化。我们的研究提供了研究GBM开发和治疗的新颖方面。

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