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. 2021 Jul 9;100(27):e26428.
doi: 10.1097/MD.0000000000026428.

Identification of potential core genes in esophageal carcinoma using bioinformatics analysis

Xiaojie Yang  1 , Mengyue Tian  2 , Weiguang Zhang  1 , Tianci Chai  3   4 , Zhimin Shen  1 , Mingqiang Kang  1 , Jiangbo Lin  1
Affiliations

Identification of potential core genes in esophageal carcinoma using bioinformatics analysis

Xiaojie Yang et al. Medicine (Baltimore). .

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a common human malignancy worldwide. The tumorigenesis mechanism in ESCC is unclear.

Materials and methods: 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).

Results: 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.

Conclusion: DEGs and hub genes were confirmed in our study, providing a thorough, scientific and comprehensive research goals for the pathogenesis of ESCC.

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Conflict of interest statement

The authors have no conflicts of interests to disclose.

Figures

Figure 1
Figure 1
Venn diagram of DEGs common to all 3 GEO datasets. (A) Upregulated genes. (B) Downregulated genes.
Figure 2
Figure 2
Protein–protein interaction network constructed with the differentially expressed genes. Note: Red nodes represent upregulated genes and green nodes represent downregulated genes.
Figure 3
Figure 3
Venn diagram of the hub genes common to the 4 groups of the top 20 genes evaluated by MCC, MNC, Degree, and Stress by the cytoHubba in Cytoscape software. And we got 6 hub genes.
Figure 4
Figure 4
Analysis of messenger RNA (mRNA) levels of the hub genes in ESCC and normal tissues from the database ENCORI and GEPIA. (A): Level of mRNA of the hub genes from the database ENCORI; (B): Level of mRNA of the hub genes from the database GEPIA.
Figure 5
Figure 5
Validation the expression of the hub genes on translational level by the Human Protein Atlas database. (A) CCNB1, (B) CDK1, (C) AURKA, (D) UBE2C, (E) CCNA2, (F) CDC20. The staining strengths were annotated as not detected, Low, Medium and High.
Figure 6
Figure 6
Correlation between expression of the hub genes and tumor stage in ESCA patients from GEPIA. Pr (>F) < .05 was considered statistically significant.
Figure 7
Figure 7
Prognostic value of 6 hub genes in ESCA. (A) Overall Survival for the hub genes in ENCORI database. The survival curve comparing the patients with high (green) and low (brown) expression in ESCA. (B) Overall Survival for the hub genes in GEPIA database. (C) Disease Free Survival for the hub genes in GEPIA database. The survival curve comparing the patients with high (red) and low (blue) expression in ESCA. P < .05 was considered statistically significant.
Figure 8
Figure 8
Correlation between hub genes expression and immune cell populations (B Cell, CD8+ T Cell, CD4+ T Cell, Macrophage, Neutrophil, and Dendritic Cell) in ESCA. P < .05 was considered statistically significant.
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