ArticleFrontiers in oncology2026
Identification of key genes potentially associated with bladder cancer development by common plasticizers: an integrated transcriptomics and network toxicology study.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Bladder cancer (BCa) is a prevalent urological malignancy. The relationship between plasticizers and BCa remains to be elucidated. The present study aimed to investigate the potential relationship between BCa and plasticizers. Methods: BCa-related data were obtained from public databases. We performed simultaneous prediction of plasticizer toxicity, as well as identification of plasticizer-related genes (PRGs) and BCa-related target genes (BCRTGs). Key genes were then identified via machine learning and the expression of the screened genes was detected using qRT-PCR. We explored the effects of key genes in BCa tumorigenesis by gene set enrichment analysis (GSEA) and constructing a molecular regulatory network using Cytoscape software. Molecular docking and molecular dynamics (MD) simulation were employed to assess the binding affinity between plasticizers and key genes. Finally, the immune microenvironment of BCa was explored. Principal results: The comprehensive data set contains a total of 4,642 differentially expressed genes. In addition, 225 PRGs and 196 BCRTGs were obtained from various online databases, and then seven candidate genes were obtained. Functional analyses revealed key potential mechanisms in BCa, such as the cell differentiation-related pathways and PI3K-Akt signaling pathway. Furthermore, five key genes (CCNE1, KIT, BCL2, TGFBR2, FASN) were then identified. In comparison to normal cells, FASN and CCNE1 exhibited elevated expression levels, while KIT, BCL2, and TGFBR2 demonstrated reduced expression in BCa cells. GSEA revealed that a subset of genes were co-enriched in cell cycle regulation. Molecular regulatory network showed that key genes have shared microRNAs (miRNAs) and TFs between them. Molecular docking and MD simulations demonstrated favorable binding affinities between the proteins encoded by the five key genes and the 3 plasticizers. Further findings revealed dysregulated infiltration levels of immune cells, including activated B cells, in BCa. Major conclusions: Five genes (CCNE1, KIT, BCL2, TGFBR2, FASN) were identified. This study used bioinformatics and network pharmacology to generate hypotheses about the possible molecular mechanisms underlying the association between plasticizer exposure and BCa, offering insights for new therapeutic approaches.
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