DEHP-associated toxic targets in endometrial carcinoma: prognostic value and immunological implications

Diethylhexyl phthalate (DEHP), a common plasticizer, has been associated with hormone disruption and carcinogenesis, but its molecular impact on uterine corpus endometrial carcinoma (UCEC) remains unclear. This study aims to computationally identify a gene signature based on known DEHP-associated toxic targets and evaluates their clinical and immunological relevance in UCEC. DEGs were intersected with DEHP targets from CTD and TargetNet databases. PPI networks, functional enrichment, and survival analyses were conducted. Prognostic genes were identified using Cox and LASSO regression. DEHP risk score models and nomograms were constructed. Immune infiltration was analyzed using ESTIMATE and ssGSEA algorithms. Molecular docking was performed via CB-Dock2. Seventy-five genetic targets linked to DEHP in toxicological databases were identified, and enrichment analyses revealed DEHP-related genes enriched in neurotransmission and hormone signaling pathways. Seven prognostic genes (HTR3A, GRM2, HTR6, THRB, TUBB2B, FOLH1, PGR) correlated with overall survival and histologic grade. The DEHP risk score effectively stratified patients. DEHP-THRB showed strongest binding affinity, suggesting direct toxicological interaction. This study characterizes a computationally derived gene signature associated with DEHP toxicity in UCEC, highlighting their prognostic and immunological significance as potential molecular footprints, while acknowledging that direct exposure inference requires future validation with measured biomonitoring data.