Phthalates- Thyroid cancer

First, the potential toxicity of phthalates was evaluated using online toxicity prediction platforms. Toxicological targets were retrieved from SwissTargetPrediction, ChEMBL, and STITCH databases and subsequently consolidated. Potential targets were then screened using a network toxicology approach, while thyroid cancer-related genes were comprehensively collected from the GeneCards database. Using R language and associated packages, the intersection of these two gene sets was identified as candidate key genes, and their biological functions were elucidated through KEGG pathway and Gene Ontology (GO) functional enrichment analyses. The candidate genes were then imported into the STRING database to construct a protein-protein interaction (PPI) network, which was further visualized using Cytoscape. Through calculations with CytoHubba and MCODE plugins, the top 20 hub genes and highly interconnected core subnetwork modules were identified. To verify the causal relationship between the intersecting genes and thyroid cancer, Mendelian Randomization (MR) analysis was performed using data from the thyroid cancer-related datasets in FinnGen database. Finally, molecular docking of phthalate esters against thyroid cancer-related key proteins was conducted, followed by molecular dynamics simulations.