Fig 1.
Identification of differentially expressed genes (DEGs) in three gene expression omnibus (GEO) datasets.
(a) Volcano plot of DEGs in GSE119056. (b) Volcano plot of DEGs in GSE54388. (c) Volcano plot of DEGs in GSE66957. Red, blue and gray color represent relatively high, low and equal expression of genes in the corresponding group, respectively. (d) Venn diagram of 265 overlapping up-regulated genes from intersection of three independent GEO datasets. p < 0.05 and |log FC |>1 were set as the threshold. (e) Venn diagram of 41 overlapping down-regulated genes from intersection of three independent GEO datasets. p < 0.05 and |log FC |>2 were set as the threshold.
Fig 2.
GO analysis and KEGG pathway analysis of the overlapping DEGs.
(a) Top 10 of biological process. (b) Top 10 of cellular component. (c) Top 10 of molecular function. (d) Top 10 of KEGG pathway enrichment.
Fig 3.
Protein-protein interactions (PPI) network, module analysis, and hub gene identification.
(a) PPI network of overlapping differentially expressed genes was constructed in STRING database. (b-c) Top two modules screened using Molecular Complex Detection (MCODE) in Cytoscape software. (d) Top twenty hub genes selected by the CytoHubba in Cytoscape based on the degree of each protein node.
Table 1.
Top 20 hub genes in network ranked by MCC method.
Table 2.
Literature retrieval of the top 20 Hub genes in three GSE datasets.
Fig 4.
Validation of hub gene expression levels in GEO.
The expression of CDC45, CDCA5, KIF4A, and ESPL1 in EOC tissues were significantly elevated compared with adjacent ovarian tissues. (a) CDC45; (b) CDCA5; (c) KIF4A; (d) ESPL1; *p < 0.05.
Fig 5.
Validation of hub gene expression levels in GEPIA.
The expression of CDC45, CDCA5, KIF4A, and ESPL1 in EOC tissues were significantly elevated compared with adjacent ovarian tissues. (a) CDC45; (b) CDCA5; (c) KIF4A; (d) ESPL1; *p < 0.05.
Fig 6.
The expression level of hub genes in EOC tissues at different stages.
To further verify the expression level of the hub genes in EOC tissues at different stages, the hub genes were analyzed by the GEPIA2 online database. ANOVA was performed to assess the statistical significance of the variations. Pr (>F) < 0.05 was considered statistically significant. According to the result, there were significant variations in the expression levels of CDC45, CDCA5, KIF4A, and ESPL1 (a-d). The overall trends indicated that the expression of these four genes decreased gradually with the continuous progression of OC.
Fig 7.
Overall survival and progression-free survival curves of DEGs in patients with EOCs from TCGA database.
The relatively higher expression of CDC45 had no statistical influence on patients’ overall survival. (b) The relatively higher expression of CDCA5 was associated with poor prognosis of EOC patients. (c) The relatively higher expression of KIF4A had no statistical influence on patients’ overall survival. (d) The relatively higher expression of ESPL1 was associated with poor prognosis of EOC patients. (e) The relatively higher expression of CDC45 had no statistical influence on patients’ progression-free survival. (f) The relatively higher expression of CDCA5 was associated with poor prognosis of EOC patients. (g) The relatively higher expression of KIF4A had no statistical influence on patients’ progression-free survival. (h) The relatively higher expression of ESPL1 was associated with poor prognosis of EOC patients.
Fig 8.
Flowchart illustrating the process of our research.