Development of Multiscale Transcriptional Regulatory Network in Esophageal Cancer Based on Integrated Analysis

Development of Multiscale Transcriptional Regulatory Network in Esophageal Cancer Based on Integrated Analysis
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基于整合分析的食管癌多尺度转录调控网络的发展

DOI:
10.1155/2020/5603958
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发表时间:
2020-08
影响因子:
--
通讯作者:
Bentong Yu
Bentong Yu
中科院分区:
生物学3区
文献类型:
--
作者:
Zihao Xu;Zilong Wu;Jingtao Zhang;Ruihao Zhou;Jiane Wu;Bentong Yu

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目的探讨多尺度综合分析方法识别食道癌关键调控因子(ESCA)。方法我们从癌症基因组图谱(TCGA)数据库下载ESCA数据集,其中包含RNA-seq数据、miRNA-seq数据、甲基化数据和临床表型信息。然后,我们结合NCBI-gene和OMIM数据库中的ESCA相关基因和TCGA中的RNA-seq数据集来分析差异表达基因(Deg)。同时,鉴定了差异表达的miRNAs(DEmiRNAs)和甲基化水平不同的基因。透视模块对是使用RAID v2.0数据库和TRRUST v2数据库建立的。在此基础上,构建了多因素调控的功能网络。此外,从DrugBank数据库中获得了与基因对应的靶向药物信息。此外,我们通过评估它们的诊断价值和预后价值,特别是区分TNM I期患者和正常患者的价值,进一步筛选了调节剂。此外,还使用了来自基因表达总览(GEO)数据库的外部数据库进行验证。最后,进行基因集浓缩分析(GSEA),以探索关键调控因子的潜在生物学功能。结果CXCL8、CYP2C8和E2F1具有较好的诊断和预后价值,可能是ESCA的潜在调节因子。同时,三种调节剂良好的早期诊断能力也为ESCA患者的诊断和早期治疗提供了新的见解。结论我们进行了多尺度综合分析,提示CXCL8、CYP2C8和E2F1在ESCA中具有良好的诊断和预后价值。
Objective To explore multiscale integrated analysis methods in identifying key regulators of esophageal cancer (ESCA). Methods We downloaded the ESCA dataset from The Cancer Genome Atlas (TCGA) database, which contained RNA-seq data, miRNA-seq data, methylation data, and clinical phenotype information. Then, we combined ESCA-related genes from the NCBI-GENE and OMIM databases and RNA-seq dataset from TCGA to analyze differentially expressed genes (DEGs). Meanwhile, differentially expressed miRNAs (DEmiRNAs) and genes with differential methylation levels were identified. The pivot–module pairs were established using the RAID v2.0 database and TRRUST v2 database. Next, the multifactor-regulated functional network was constructed based on the above information. Additionally, gene corresponding targeted drug information was obtained from the DrugBank database. Moreover, we further screened regulators by assessing their diagnostic value and prognostic value, especially the value of distinguishing patients at TNM I stage from normal patients. In addition, the external database from the Gene Expression Omnibus (GEO) database was used for validation. Lastly, gene set enrichment analysis (GSEA) was performed to explore the potential biological functions of key regulators. Results Our study indicated that CXCL8, CYP2C8, and E2F1 had excellent diagnostic and prognostic values, which may be potential regulators of ESCA. At the same time, the good early diagnosis ability of the three regulators also provided new insights for the diagnosis and early treatment of ESCA patients. Conclusion We develop a multiscale integrated analysis and suggest that CXCL8, CYP2C8, and E2F1 are promising regulators with good diagnostic and prognostic values in ESCA.
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