To identify biomarkers associated with the transfer of diabetes combined with cancer in human genes using bioinformatics analysis

Abstract

Currently, the incidence of diabetes mellitus is increasing rapidly, particularly in China, and its pathogenesis is still unclear. The goal of this study was to find meaningful biomarkers of metastasis in patients with diabetes and cancer using bioinformatic analysis in order to predict gene expression and prognostic importance for survival. We used the Differentially Expressed Gene, Database for Annotation Visualization and Integrated Discovery, and Gene Set Enrichment Analyses databases, as well as several bioinformatics tools, to explore the key genes in diabetes. Based on the above database, we ended up with 10 hub genes (FOS, ATF3, JUN, EGR1, FOSB, JUNB, BTG2, EGR2, ZFP36, and NR4A2). A discussion of the 10 critical genes, with extensive literature mentioned to validate the association between the 10 key genes and patients with diabetes and cancer, to demonstrate the importance of gene expression and survival prognosis. This study identifies several biomarkers associated with diabetes and cancer development and metastasis that may provide novel therapeutic targets for diabetes combined with cancer patients.

Figure 1.

Volcano plots of DEGs detected from the datasets of GSE29226 and GSE29231. (A) GSE29226, (B) GSE29231. The red dots represent upregulated DEGs; the green dots mean downregulated DEGs; the black dots denote no differentially expressed genes. DEG = differentially expressed gene.

Figure 2.

Identification of DEGs associated with DM metastasis. (A) The Venn diagram demonstrates the crossed genes shared by GSE29226 and GSE29231 datasets. The left panel represents the downregulated intersectional expressed genes between GSE29226 and GSE29231 datasets, whereas the right panel represents the upregulated co-differentially genes between the 2 datasets. (B) Heatmap of the top 63 DEGs associated with DM metastasis in the 2 datasets. Left, GSE29226; right, GSE29231. DEG = differentially expressed gene, DM = diabetes mellitus.

Figure 3.

GO and KEGG pathway enrichment analyses of DEGs using the DAVID database. (A) Biological processes, cellular components, molecular functions, and (B) the signaling pathways from the GSE29226 and GSE29231 datasets. DAVID = database for annotation visualization and integrated discovery, DEG = differentially expressed gene, GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes.

Figure 4.

PPI network analysis and identification of hub genes. (A) Protein-protein interactions of DEGs were analyzed using the STRING database. (B) Sankey diagram of DM: The picture demonstrates 63 genes and pathways associated with DM. DEG = differentially expressed gene, DM = diabetes mellitus, PPI = protein-protein interaction, STRING = search tool for the retrieval of interacting genes.

Figure 5.

GO analyses of DEGs in the most significant module using Cytoscape plugins ClueGO and CluePedia. (A) Percentages of biological processes terms per group. (B) Percentages of cellular components terms per group. (C) Percentages of molecular functions terms per group. (D) Percentages of Kyoto Encyclopedia of Genes and Genomes terms per group. DEG = differentially expressed gene, GO = gene ontology.

Figure 6.

Significantly enriched GO and KEGG pathways for the 10 hub genes using the WebGestalt database. (A) 10 hub genes were identified from the most significant module. (B) Biological process, (C) Cellular component, (D) Molecular function, (E) KEGG pathways for the 10 hub genes. GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes.

Figure 7.

Validation of the 10 hub genes overexpression in DM metastasis using the GEPIA database. *P < .05, unpaired Student t test. DM = diabetes mellitus, GEPIA = Gene Expression Profile Interaction Analysis.

Figure 8.

Kaplan–Meier curves for overall survival analysis of the 10 hub genes in DM patients. The red line represented the high expression group, whereas the black line denoted the low expression group. DM = diabetes mellitus.

Figure 9.

Kaplan–Meier curves for recurrence-free survival analysis of the 10 hub genes in DM patients. The red line represented the high expression group, whereas the black line denoted the low expression group. DM = diabetes mellitus.