Identification of key candidate genes and pathways in endometrial cancer: Evidence from bioinformatics analysis

Abstract

Endometrial cancer (EC) is the fourth most common cancer in women worldwide. Although researchers are exploring the biological processes of tumorigenesis and development of EC, the gene interactions and biological pathways of EC are not accurately verified. In the present study, bioinformatics methods were used to screen for key candidate genes and pathways that were associated with EC and to reveal the possible mechanisms at molecular level. Microarray datasets (GSE63678, GSE17025 and GSE3013) from the Gene Expression Omnibus database were downloaded and 118 differentially expressed genes (DEGs) were selected using a Venn diagram. Functional enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed, including the module analysis. A total of 11 hub genes were identified from the DEGs, and functional enrichment analyses were performed to clarify their possible biological processes. A total of 118 DEGs were selected from three mRNA datasets. Functional enrichment demonstrated 27 downregulated genes that were primarily involved in the positive regulation of transcription from RNA polymerase II promoter, protein binding and the nucleus. A total of 91 upregulated DEGs were mainly associated with cell division, protein binding and the nucleus. Pathway analysis indicated that the downregulated DEGs were mainly enriched in pathways associated with cancer, and the upregulated DEGs were mainly enriched in the cell cycle. The 11 hub genes were primarily enriched in the cell cycle, oocyte meiosis, progesterone-mediated oocyte maturation, the p53 signaling pathway and viral carcinogenesis. The integrated analysis showed that cyclin B1, ubiquitin conjugating enzyme E2 C and cell division cycle 20 may participate in the tumorigenesis, development and invasion of EC. In conclusion, the hub genes and pathways identified in the present study contributed to the understanding of carcinogenesis and progression of EC at the mechanistic and molecular-biological level. As candidate targets for the diagnosis and treatment of EC, these genes deserve further investigation.

Keywords: Gene Expression Omnibus database; bioinformatics analysis; differentially expressed genes; endometrial cancer.

Figure 1.

Venn diagram of DEGs. DEGs were selected with a fold change >1 and adjusted P-value <0.05 among the mRNA expression profiling sets GSE63678, GSE17025 and GSE3013. The three datasets showed an overlap of 118 genes. DEGs, differentially expressed genes.

Figure 2.

The GO terms of the BP, CC and MF categories enrichment of the 118 differentially expressed genes. (A) Upregulated gene enrichment in GO. (B) Downregulated gene enrichment in GO. GO, Gene Ontology; BP, biological process; CC, cellular component; MF, molecular function.

Figure 3.

The KEGG pathway analysis of the 118 differentially expressed genes. The KEGG pathway analysis of (A) upregulated genes and (B) downregulated genes. KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 4.

PPI network of the 118 DEGs. (A) The PPI network of the 118 DEGs, the most significant module was shown in red. (B) The PPI network of the 11 hub genes (degree ≥45). DEGs, differentially expressed genes; PPI, protein-protein interaction.

Figure 5.

A network of the hub genes and their co-expression genes. Nodes with bold black outline represent hub genes. Nodes with thin black outline represent the co-expression genes.

Figure 6.

The biological process analysis of the hub genes. The color depth of nodes refers to the corrected P-value of ontologies. The size of nodes refers to the numbers of genes that are involved in the ontologies.

Figure 7.

Hierarchical clustering of hub genes was constructed by University of California Santa Cruz. The samples under the brown bar are non-cancerous samples and the samples under the blue bar are endometrial cancer samples. Upregulated genes are marked in red; downregulated genes are marked in blue.

Figure 8.

Overall survival and disease-free survival analyses of hub genes. Overall survival (A) and disease-free survival analyses (B) of hub genes were performed using cBioPortal online platform. P<0.05 was considered statistically significant.

Figure 9.

The expression profile of CCNB1, UBE2C and CDC20 in human tissues. Gene expression in tumor tissue (marked in red) and in normal tissue (marked in green). The darker the color the higher expression. CCNB1, cyclin B1; UBE2C, ubiquitin conjugating enzyme E2 C; CDC20, cell division cycle 20.

Figure 10.

Analysis of CCNB1, UBE2C and CDC20 expression in different tissues by UALCAN. CCNB1, cyclin B1; UBE2C, ubiquitin conjugating enzyme E2 C; CDC20, cell division cycle 20.