Assessing the toxicological impact of DEGDB plasticizer exposure on glioblastoma multiforme via network toxicology, machine learning and in vitro methods

Abstract

Diethylene glycol dibenzoate (DEGDB) is a novel environmentally friendly plasticizer. However, toxicological studies on DEGDB remain limited, and its potential harmful effects on the malignant progression of glioblastoma are still unclear. Further systematic evaluation of its toxicity is warranted. The network toxicology, machine learning algorithm and molecular docking techniques were used to study the toxicological mechanisms of DEGDB-induced glioblastoma multiforme (GBM). The five core targets (CEBPB, CNR1, FASN, NPY and SCD) were screened out by ChEMBL, PubChem, SwissADME, CTD, STRING, TCGA and GTEx databases. GO and KEGG pathway enrichment analyses suggested that DEGDB could affect cancer and immune related pathways. The multi-level evidence for core genes was provided in GBM as potential molecular biomarkers. The TCGA, GEPIA, UALCAN, KM plotter, and TIMER databases were used to evaluate the prognosis of five core targets in GBM. The expression of CEBPB, SCD and age were shown as independent prognostic factors in GBM progression. The expression level of five core genes were significantly associated with the immune microenvironment. Molecular docking technology confirmed the strong binding affinity of DEGDB with five core targets. Moreover, DEGDB could stimulate proliferation on GBM cells, and significantly affect the protein expression levels of CEBPB and SCD. To sum up, DEGDB may accelerate the malignant progression of GBM by regulating cell proliferation, fatty acid metabolism, and immune response. These studies will provide a theoretical basis for preventing malignant diseases progression and for evaluating the related health risk strategies of novel plasticizers.