Diabetes mellitus induces a novel inflammatory network involving cancer progression: Insights from bioinformatic analysis and in vitro validation

Abstract

Abstract Background The diabetes patients have a higher incidence of malignant tumors than people without diabetes. However, the molecular mechanisms of the relationship between diabetes and malignant tumors remain largely unknown. Methods By exploiting available public databases, diabetes and cancer-related genes (DCRGs) were screened, and a diabetes-based cancer-associated inflammation network (DCIN) was constructed. Then, the role of DCRGs in different tumors were analyzed from various perspectives. Additionally, drug sensitivity and single-cell sequencing data were analyzed using colon cancer (COAD) as an example. Finally, the expression of DCRGs and arachidonic acid metabolism pathway was verified in vitro. Results Seven identified DCRGs, including PPARG, MMP9, CTNNB1, TNF, TGFB1, PTGS2, and HIF1A, were integrated to construct a DCIN. The bioinformatics analysis showed that the expression of the seven DCRGs in different tumors was significantly different, which had varied effects on diverse perspectives. Single-cell sequencing analyzed in COAD showed that the activity of the DCRGs was highest in M1 macrophage and the lowest in Plasma B. In vitro experiments showed that the DCRGs verified by western bolt and PEG2 verified by ELISA were all highly expressed in COAD epithelial cells stimulated by high glucose. Conclusion This study, for the first time, constructed a DCIN, which provides novel insights into the underlying mechanism of how diabetes increases the occurrence and development of tumors. Although further research is required, our results offer clues for new potential therapeutic strategies to prevent and treat malignant tumors.