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, and thyroid cancer (THCA), the most common endocrine malignancy, has 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. These genes were subsequently subjected to Mendelian randomization (MR) analysis to identify those with causal links to THCA. By integrating 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 using 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 enhancing monitoring of PPCP pollution and offer valuable implications for THCA prevention and therapeutic strategy development.