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Weighted Gene Coexpression Network Analysis Reveals the Dynamic Transcriptome Regulation and Prognostic Biomarkers of Hepatocellular Carcinoma
Evolutionary Bioinformatics ( IF 2.6 ) Pub Date : 2020-05-18 , DOI: 10.1177/1176934320920562
Shuping Qu 1 , Qiuyuan Shi 2 , Jing Xu 3 , Wanwan Yi 2 , Hengwei Fan 1
Affiliation  

This study was aimed at revealing the dynamic regulation of mRNAs, long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in hepatocellular carcinoma (HCC) and to identify HCC biomarkers capable of predicting prognosis. Differentially expressed mRNAs (DEmRNAs), lncRNAs, and miRNAs were acquired by comparing expression profiles of HCC with normal samples, using an expression data set from The Cancer Genome Atlas. Altered biological functions and pathways in HCC were analyzed by subjecting DEmRNAs to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Gene modules significantly associated with disease status were identified by weighted gene coexpression network analysis. An lncRNA-mRNA and an miRNA-mRNA coexpression network were constructed for genes in disease-related modules, followed by the identification of prognostic biomarkers using Kaplan-Meier survival analysis. Differential expression and association with the prognosis of 4 miRNAs were verified in independent data sets. A total of 1220 differentially expressed genes were identified between HCC and normal samples. Differentially expressed mRNAs were significantly enriched in functions and pathways related to “plasma membrane structure,” “sensory perception,” “metabolism,” and “cell proliferation.” Two disease-associated gene modules were identified. Among genes in lncRNA-mRNA and miRNA-mRNA coexpression networks, 9 DEmRNAs and 7 DEmiRNAs were identified to be potential prognostic biomarkers. MIMAT0000102, MIMAT0003882, and MIMAT0004677 were successfully validated in independent data sets. Our results may advance our understanding of molecular mechanisms underlying HCC. The biomarkers may contribute to diagnosis in future clinical practice.



中文翻译:

加权基因共表达网络分析揭示了肝细胞癌的动态转录组调控和预后生物标志物。

这项研究的目的是揭示肝细胞癌(HCC)中mRNA,长非编码RNA(lncRNA)和microRNA(miRNA)的动态调控,并鉴定能够预测预后的HCC生物标记物。使用来自癌症基因组图谱的表达数据集,通过比较HCC和正常样品的表达谱,获得差异表达的mRNA(DEmRNA),lncRNA和miRNA。通过对DEmRNA进行基因本体论和《京都议定书》基因与基因组分析,分析了肝癌中生物学功能和途径的变化。通过加权基因共表达网络分析鉴定与疾病状况显着相关的基因模块。为疾病相关模块中的基因构建了lncRNA-mRNA和miRNA-mRNA共表达网络,然后使用Kaplan-Meier生存分析识别预后生物标志物。在独立的数据集中验证了4种miRNA的差异表达及其与预后的关系。在肝癌和正常样本之间共鉴定出1220个差异表达基因。差异表达的mRNA在与“质膜结构”,“感觉知觉”,“代谢”和“细胞增殖”有关的功能和途径中显着丰富。确定了两个与疾病相关的基因模块。在lncRNA-mRNA和miRNA-mRNA共表达网络中的基因中,有9个DEmRNA和7个DEmiRNA被鉴定为潜在的预后生物标志物。MIMAT0000102,MIMAT0003882和MIMAT0004677已在独立数据集中成功验证。我们的结果可能会加深我们对肝癌潜在分子机制的了解。生物标志物可能有助于未来临床实践中的诊断。

更新日期:2020-06-30
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