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

in Environmental pollution (Barking, Essex : 1987) by Yintao Ye, Wei Zhong, Lijuan Liang, Ruyi Han, Jiangeng Han, Chunwei Wang, Lei Chen, Junqiang Qian

TLDR

  • This study explores the toxicological mechanisms of DEGDB-induced glioblastoma multiforme (GBM) and its potential impact on malignant progression.

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.

Overview

  • The study aimed to investigate the toxicological mechanisms of DEGDB-induced glioblastoma multiforme (GBM) and its potential impact on malignant progression.
  • The authors screened five core targets (CEBPB, CNR1, FASN, NPY, and SCD) and used network toxicology, machine learning algorithms, and molecular docking techniques to study DEGDB's toxicological mechanisms.
  • The study aimed to identify potential molecular biomarkers for GBM and evaluate the prognosis of five core targets in GBM.

Comparative Analysis & Findings

  • GO and KEGG pathway enrichment analyses suggested that DEGDB affects cancer and immune-related pathways.
  • The multi-level evidence for core genes was provided in GBM as potential molecular biomarkers, with CEBPB, SCD, and age shown as independent prognostic factors in GBM progression.
  • The expression level of five core genes was significantly associated with the immune microenvironment, and molecular docking technology confirmed the strong binding affinity of DEGDB with five core targets.

Implications and Future Directions

  • The study suggests that DEGDB may accelerate the malignant progression of GBM by regulating cell proliferation, fatty acid metabolism, and immune response, which could provide a theoretical basis for preventing malignant disease progression and evaluating the related health risk strategies of novel plasticizers.
  • Future studies should consider the limitations of this study, such as the limited sample size and lack of in vivo experiments, to provide a more comprehensive understanding of DEGDB's toxicological mechanisms and potential impacts on GBM.
  • The findings of this study could be used to develop novel therapeutic strategies for GBM treatment and to explore the potential applications of DEGDB as a cancer therapeutic agent.
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