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Mutations in gliclazide‐associated genes may predict poor bladder cancer prognosis

机译：格列齐特相关基因的突变可能预示膀胱癌的不良预后

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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.
机译：近年来，越来越多的患者同时患有糖尿病和癌症。因此，对于医生而言，选择具有最低诱发癌症风险的降血糖药物至关重要。格列齐特是一种广泛使用的磺酰脲降糖药，但其癌症风险仍存在争议。在这里，我们通过查询可用的数据库来构建生物网络，探索了格列齐特及其相关基因的主要靶标。通过使用DrugBank和STRING，我们发现了格列齐特和50个格列齐特相关基因的两个主要靶标，然后使用WebGestalt进行了京都基因和基因组百科全书（KEGG）富集分析。通过此分析，我们获得了前15个KEGG途径。对这些KEGG通路的准确分析显示，有两条通路与格列齐特在功能上相关，其中一条通路与膀胱癌有关，而另一条通路与磷酸肌醇3激酶-AKT信号通路有关。最后，使用cBioPortal进行的基因组分析表明，这四个重叠基因的基因组改变预示了膀胱癌患者的不良预后。总之，格列齐特应谨慎用作糖尿病癌症患者（尤其是膀胱癌）的降血糖药物。此外，这项研究提供了功能网络分析，可以灵活地探索药物相互作用系统并评估其安全性。

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