Bioinformatics analysis to identify endocrine-disrupting chemicals targeting key ESCC-related genes

Esophageal squamous cell carcinoma (ESCC), which has a high incidence and mortality rate in East Asia, arises from a complex interplay between genetic alterations and environmental exposures. Among environmental risk factors, endocrine-disrupting chemicals (EDCs) have attracted widespread attention, yet their impact on ESCC <i>via</i> gene interactions remains underexplored. This study integrated bioinformatics analysis to identify key genes and EDCs associated with ESCC pathogenesis. Chemical–gene interaction data were obtained from the Comparative Toxicogenomics Database(CTD), and differentially expressed genes(DEGs) were screened from the Gene Expression Omnibus (GEO) database. LASSO regression analysis prioritized five key genes (<i>BUB1B</i>, <i>TPM2</i>, <i>KRT17</i>, <i>ADH1B</i>, <i>SALL4</i>). Based on these genes, 25 EDCs potentially involved in ESCC were identified, of which 13 (such as benzo[a]pyrene) targeted at least three of the key genes. These findings suggested a novel EDC–gene–ESCC interaction network and provide insights into the environmental mechanisms underlying ESCC, offering potential targets for risk assessment and therapeutic intervention.