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采用综合分析方法鉴定间变性甲状腺癌中的关键通路和生物标志物。

Identification of key pathways and biomarkers in anaplastic thyroid cancer using an integrated analysis.

机构信息

Department of Clinical Medicine, The Second Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China.

出版信息

J BUON. 2020 Nov-Dec;25(6):2690-2699.

PMID:33455115
Abstract

PURPOSE

Thyroid carcinoma (THCA) is one of the most common endocrine tumours with high morbidity worldwide. Anaplastic thyroid cancer (ATC) is the most fatal and has the poorest prognosis of the four THCA types, as it lacks effective treatments. Early screening of ATC is problematic and so identifying ATC biomarkers is increasingly crucial.

METHODS

We performed a systematic search of the thyroid transcriptome in the Gene Expression Omnibus (GEO) database and an integrative analysis of gene expression profiles. Moreover, we conducted a pathway enrichment analysis in ATC using the WEB-based GEne SeT AnaLysis Toolkit. We identified the intersections of all the differentially expressed genes (DEGs) between ATC and normal samples and DEGs between ATC and non-ATC samples in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Finally, we used Cytoscape software to visualize the protein-protein interaction (PPI) network.

RESULTS

Six gene expression datasets containing 131 thyroid cancer samples and 98 normal control samples were collected to identify the significant DEGs. A total of 1489 DEGs were identified between ATC and normal samples, and 522 DEGs between ATC and non-ATC samples. ATC showed a greater association with the cell cycle. The Principal component analysis (PCA) results revealed 222 genes with substantial contributions to the identification of ATC.

CONCLUSION

Cell cycle plays a decisive role in the high mortality rate of ATC. TOP2A, NUSAP1, PBK, KIF15, CENPF, CEP55, CDK1, CCNB2, CDCA8 and CDC20 were identified as hub genes.

摘要

目的

甲状腺癌(THCA)是全球发病率较高的最常见内分泌肿瘤之一。间变性甲状腺癌(ATC)是四种 THCA 类型中最致命的,预后最差,因为它缺乏有效治疗方法。ATC 的早期筛查存在问题,因此识别 ATC 的生物标志物变得越来越重要。

方法

我们在基因表达综合数据库(GEO)中对甲状腺转录组进行了系统搜索,并对基因表达谱进行了综合分析。此外,我们使用基于网络的基因集分析工具包(WEB-based GEne SeT AnaLysis Toolkit)对 ATC 进行了途径富集分析。我们确定了 ATC 与正常样本以及 ATC 与非 ATC 样本之间所有差异表达基因(DEG)之间的交集。最后,我们使用 Cytoscape 软件可视化蛋白质-蛋白质相互作用(PPI)网络。

结果

共收集了 6 个包含 131 个甲状腺癌样本和 98 个正常对照样本的基因表达数据集,以鉴定显著的 DEG。在 ATC 与正常样本之间共鉴定出 1489 个 DEG,在 ATC 与非 ATC 样本之间鉴定出 522 个 DEG。ATC 与细胞周期的相关性更大。主成分分析(PCA)结果显示,有 222 个基因对 ATC 的鉴定有重要贡献。

结论

细胞周期在 ATC 高死亡率中起决定性作用。TOP2A、NUSAP1、PBK、KIF15、CENPF、CEP55、CDK1、CCNB2、CDCA8 和 CDC20 被鉴定为关键基因。

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