Identification of functional genes regulating gastric cancer progression using integrated bioinformatics analysis

Figure 1 A flow diagram of the present study. GEO: Gene Expression Omnibus; DEG: Differentially expressed gene; DAVID: Database for Annotation, Visualization, and Integrated Discovery; KEGG: Kyoto Encyclopedia of Genes and Genomes; STRING: Search Tool for the Retrieval of Interacting Genes; GEPIA: Gene Expression Profiling Interactive Analysis.

Figure 2 Authentication of 251 common differentially expressed genes in the three datasets (GSE13911, GSE66229, and GSE 79973) through Venn Diagrams software. Different color represents different datasets. A: Sixty-four differentially expressed genes (DEGs) were upregulated in the three datasets (logFC > 0); B: 187 DEGs were downregulated in the three datasets (logFC < 0). DEGs: Differentially expressed genes. Available online: http://bioinformatics.psb.ugent.be/webtools/Venn/.

Figure 3 Gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of differentially expressed genes significantly enriched in gastric cancer. GO: Gene ontology.

Figure 4 Common differentially expressed genes protein-protein interaction network constructed by Search Tool for the Retrieval of Interacting Genes online database and Module analysis. A: A total of 251 differentially expressed genes (DEGs) were found in the DEGs protein-protein interaction network complex. The nodes represent proteins; the edges represent the interaction of proteins; green circles represent down-regulated DEGs and red circles represent up-regulated DEGs; B: Module analysis via Cytoscape software. PPI: Protein-protein interaction; STRING: Search Tool for the Retrieval of Interacting Genes.

Figure 5 Analysis of BIRC5, TRIP13, and UBE2C genes in patient tissues and the correlation with survival. A-C: Overall survival of gastric cancer patients with high expression and low expression of BIRC5 (A), TRIP13 (B), and UBE2C (C) genes; D-E: The expression of these genes was analyzed with GEPIA tools. ^aP < 0.05.

Figure 6 Increased level of BIRC5, TRIP13, and UBE2C genes are related to cell proliferation of gastric cancer cells. A-C: Expression of BIRC5, TRIP13, and UBE2C genes in 15 pairs of tumor and adjacent normal tissues; D-E: Knockdown of BIRC5, TRIP13, or UBE2C genes significantly suppressed cancer cell proliferation. ^aP < 0.05; ^bP < 0.01.

Figure 7 Increased level of BIRC5, TRIP13, and UBE2C genes confers cellular resistance to cisplatin in gastric cancer cells. A-C: Colony formation assay in cells with shRNA transfected targeting BIRC5, TRIP13, or UBE2C genes; D-F: Cell apoptosis was detected in BIRC5, TRIP13, and UBE2C knockdown cells after treatment with cisplatin. ^aP < 0.05; ^bP < 0.01.