Exploring the mechanism of action of PPCPs on thyroid cancer based on network toxicology, Mendelian analysis and molecular docking

Pharmaceuticals and personal care products (PPCPs) are ubiquitous environmental contaminants linked to various adverse health outcomes, while thyroid cancer (THCA) remains the most common endocrine malignancy with a globally increasing incidence. This study aimed to systematically elucidate the molecular mechanisms underlying the effects of 11 prevalent PPCPs on THCA via an integrated bioinformatics approach. Candidate target genes of the 11 PPCPs were retrieved and predicted using authoritative public databases, subsequently subjected to Mendelian randomization (MR) analysis to identify genes with causal links to THCA. Integrated with transcriptome data mining and differential expression analysis, key genes with consistent causal relationships and expression patterns were screened. Core targets were prioritized through complementary machine learning approaches and validated via independent external datasets. Functional enrichment analyses, immune infiltration assessment, single-cell RNA sequencing, and molecular docking were further performed to decipher potential regulatory mechanisms. This study delineates the core targets and pivotal molecular pathways underlying PPCP-mediated regulation of THCA progression, providing novel insights into the environmental etiology of THCA. The findings underscore the necessity of strengthening PPCP pollution monitoring and offer valuable implications for THCA prevention and therapeutic strategy development.