Zhang Zhi, Zou Zhenning, Dai Haixia, Ye Ruifang, Di Xiaoqing, Li Rujia, Ha Yanping, Sun Yanqin, Gan Siyuan
Department of Thyroid and Mammary Vascular Surgery, the Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Pathology, Guangdong Medical University, Zhanjiang, China.
Transl Cancer Res. 2020 Jul;9(7):4188-4203. doi: 10.21037/tcr-19-2829.
Since anaplastic thyroid carcinoma (ATC) has rapid progression and a poor outcome, identification of the key genes and underlying mechanisms of ATC is required.
Gene expression profiles of GSE29265 and GSE33630 were available from the Gene Expression Omnibus database. The two profile datasets included 19 ATC tissues, 55 normal thyroid tissues and 59 papillary thyroid cancer (PTC) tissues. Differentially expressed genes (DEGs) between ATC tissues and normal thyroid tissues as well as ATC tissues and PTC tissues were identified using the GEO2R tool. Common DEGs between the two datasets were selected via Venn software online. Then, we applied the Database for Annotation, Visualization and Integrated Discovery for Kyoto Encyclopedia of Gene and Genome pathway and gene ontology (GO) analyses. Additionally, protein-protein interactions (PPIs) of these DEGs were visualized via Cytoscape with Search Tool for the Retrieval of Interacting Genes. In the PPI networks analyzed by the Molecular Complex Detection plug-in, all 54 upregulated core genes were selected. Furthermore, Kaplan-Meier analysis was applied to analyze overall survival based on these 54 genes. Then, we used the DrugBank database to identify drug relationships for the 54 genes. Additionally, we validated the correlations between genes enriched in pathways and genes identified as prognosis biomarkers of THCA by Gene Expression Profiling Interactive Analysis.
Four genes ( and ) involved cell cycle arrest and DNA repair were significantly enriched in the G2/M phase of the cell cycle pathway and before G2 phase arrest of the P53 pathway. Inhibitors of CHEK1, CDK1 and TOP2A were identified in the DrugBank database. ANLN, DEPDC1, KIF2C, CENPN, TACC3 CCNB2 and CDC6 were hypothesized to be prognostic biomarkers of ATC. Furthermore, , , and were significantly positively associated with these prognosis genes.
and may be key genes involved cell cycle arrest and DNA damage repair in ATC. Further studies are required to confirm the contributions of the identified genes to ATC progression and survival.
由于间变性甲状腺癌（ATC）进展迅速且预后不良，因此需要确定ATC的关键基因及其潜在机制。
基因表达综合数据库中可获取GSE29265和GSE33630的基因表达谱。这两个谱数据集包括19个ATC组织、55个正常甲状腺组织和59个甲状腺乳头状癌（PTC）组织。使用GEO2R工具鉴定ATC组织与正常甲状腺组织以及ATC组织与PTC组织之间的差异表达基因（DEG）。通过在线Venn软件选择两个数据集之间的共同DEG。然后，我们应用基因与基因组京都百科全书通路注释、可视化和综合发现数据库以及基因本体（GO）分析。此外，这些DEG的蛋白质-蛋白质相互作用（PPI）通过Cytoscape与相互作用基因检索搜索工具进行可视化。在通过分子复合物检测插件分析的PPI网络中，选择了所有54个上调的核心基因。此外，应用Kaplan-Meier分析基于这54个基因分析总生存期。然后，我们使用药物银行数据库确定这54个基因的药物关系。此外，我们通过基因表达谱交互分析验证了富集在通路中的基因与被鉴定为THCA预后生物标志物的基因之间的相关性。
涉及细胞周期停滞和DNA修复的四个基因在细胞周期通路的G2/M期和P53通路的G2期停滞之前显著富集。在药物银行数据库中鉴定出了CHEK1、CDK1和TOP2A的抑制剂。假设ANLN、DEPDC1、KIF2C、CENPN、TACC3、CCNB2和CDC6是ATC的预后生物标志物。此外，[此处原文缺失具体基因名称]与这些预后基因显著正相关。
[此处原文缺失具体基因名称]可能是参与ATC细胞周期停滞和DNA损伤修复的关键基因。需要进一步研究以证实所鉴定基因对ATC进展和生存的作用。
