Department of Thoracic Surgery.
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Medicine (Baltimore). 2021 Jul 9;100(27):e26428. doi: 10.1097/MD.0000000000026428.
Esophageal squamous cell carcinoma (ESCC) is a common human malignancy worldwide. The tumorigenesis mechanism in ESCC is unclear.
To explore potential therapeutic targets for ESCC, we analyzed 3 microarray datasets (GSE20347, GSE38129, and GSE67269) derived from the gene expression omnibus (GEO) database. Then, the GEO2R tool was used to screen out differently expressed genes (DEGs) between ESCC and normal tissue. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation, visualization and integrated discovery to identify the pathways and functional annotation of DEGs. Protein-protein interaction of these DEGs was analyzed based on the search tool for the retrieval of interacting genes database and visualized by Cytoscape software. In addition, we used encyclopedia of RNA interactomes (ENCORI), gene expression profiling interactive analysis (GEPIA), and the human protein atlas to confirm the expression of hub genes in ESCC. Finally, GEPIA was used to evaluate the prognostic value of hub genes expression in ESCC patients and we estimated the associations between hub genes expression and immune cell populations (B Cell, CD8+ T Cell, CD4+ T Cell, Macrophage, Neutrophil, and Dendritic Cell) in esophageal carcinoma (ESCA) using tumor immune estimation resource (TIMER).
In this study, 707 DEGs (including 385 upregulated genes and 322 downregulated genes) and 6 hub genes (cyclin B1 [CCNB1], cyclin dependent kinase 1 [CDK1], aurora kinase A [AURKA], ubiquitin conjugating enzyme E2C [UBE2C], cyclin A2 [CCNA2], and cell division cycle 20 [CDC20]) were identified. All of the 6 hub genes were highly expressed in ESCC tissues. Among of them, only CCNB1 and CDC20 were associated with stage of ESCC and all of them were not associated with survival time of patients.
DEGs and hub genes were confirmed in our study, providing a thorough, scientific and comprehensive research goals for the pathogenesis of ESCC.
食管鳞状细胞癌(ESCC)是一种常见的人类恶性肿瘤。ESCC 的肿瘤发生机制尚不清楚。
为了探索 ESCC 的潜在治疗靶点,我们分析了三个来自基因表达综合数据库(GEO)的微阵列数据集(GSE20347、GSE38129 和 GSE67269)。然后,使用 GEO2R 工具筛选 ESCC 和正常组织之间差异表达的基因(DEGs)。使用数据库进行注释、可视化和综合发现来进行基因本体功能和京都基因与基因组百科全书通路富集分析,以确定 DEGs 的通路和功能注释。基于搜索工具检索相互作用基因数据库分析这些 DEGs 的蛋白质-蛋白质相互作用,并通过 Cytoscape 软件可视化。此外,我们使用 RNA 相互作用百科全书(ENCORI)、基因表达谱交互式分析(GEPIA)和人类蛋白质图谱来确认 ESCC 中枢纽基因的表达。最后,使用 GEPIA 评估枢纽基因表达在 ESCC 患者中的预后价值,并使用肿瘤免疫估计资源(TIMER)估计枢纽基因表达与食管癌(ESCA)中免疫细胞群体(B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞)之间的关联。
在这项研究中,鉴定出 707 个 DEGs(包括 385 个上调基因和 322 个下调基因)和 6 个枢纽基因(细胞周期蛋白 B1 [CCNB1]、细胞周期蛋白依赖性激酶 1 [CDK1]、极光激酶 A [AURKA]、泛素结合酶 E2C [UBE2C]、细胞周期蛋白 A2 [CCNA2]和细胞分裂周期 20 [CDC20])。这 6 个枢纽基因在 ESCC 组织中均高表达。其中,只有 CCNB1 和 CDC20 与 ESCC 的分期有关,而所有这些基因与患者的生存时间均无关。
在本研究中证实了 DEGs 和枢纽基因,为 ESCC 的发病机制提供了全面、科学和综合的研究目标。