Frontiers in toxicology
Genetic evidence and multi-omics characterization of DEHP-relevant detoxification and metabolic heterogeneity in hepatocellular carcinoma
Par Fan Z, Zhang G, Ren L et 1 autres.
Contenu en anglais
Résumé
Background
Human evidence linking di(2-ethylhexyl) phthalate (DEHP) exposure to hepatocellular carcinoma (HCC) is limited, and it remains unclear whether DEHP-relevant detoxification biology captures clinically meaningful HCC heterogeneity.
Methods
We integrated two-sample Mendelian randomization, proteomic and phosphoproteomic subtyping, bulk, single-cell and spatial transcriptomics, computational candidate prioritization, molecular docking, and cell-based assays. Genetically proxied MECPP and MEHHP were evaluated for associations with HCC and liver-related outcomes. DPTS-related molecular, cellular, spatial, and experimental patterns were then characterized.