Mutations in gliclazide-associated genes may predict poor bladder cancer prognosis.

In recent years, an increasing number of patients have had diabetes and cancer simultaneously; thus, it is crucial for physicians to select hypoglycemic drugs with the lowest risk of inducing cancer. Gliclazide is a widely used sulfonylurea hypoglycemic drug, but its cancer risk remains controversial. Here, we explored the primary targets of gliclazide and its associated genes by querying an available database to construct a biological network. By using DrugBank and STRING, we found two primary targets of gliclazide and 50 gliclazide-associated genes, which were then enrolled for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using WebGestalt. From this analysis, we obtained the top 15 KEGG pathways. Accurate analysis of these KEGG pathways revealed that two pathways, one linked to bladder cancer and the other linked to the phosphoinositide 3-kinase-AKT signaling pathway, are functionally associated with gliclazide, and from these we identified four overlapping genes. Finally, genomic analysis using cBioPortal showed that genomic alterations of these four overlapping genes predict poor prognosis for patients with bladder cancer. In conclusion, gliclazide should be used with caution as a hypoglycemic drug for diabetic patients with cancer, especially bladder cancer. In addition, this study provides a functional network analysis to flexibly explore drug interaction systems and estimate their safety.