Network toxicology and single-cell analysis reveal molecular mechanisms of DEHP-induced colorectal cancer.

Di(2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant associated with colorectal cancer (CRC), but its molecular mechanisms remain unclear. Hence, we integrated toxicological target screening, weighted gene co-expression network analysis (WGCNA), and 113 machine learning algorithms to construct a diagnostic model for DEHP-related CRC. Single-cell transcriptomics and molecular docking were further applied to analyze the cellular distribution of key genes and the interactions between DEHP and target proteins. Five core genes (MMP7, CDK4, MMP1, CNR1, and TNFRSF1A) were identified and linked to inflammation, cell cycle regulation, and PI3K-Akt signaling. Thus, we report the molecular basis of DEHP-induced CRC progression providing a novel strategy for identifying environmental carcinogenic biomarkers and therapeutic targets.