Combining multi-omics analysis and network toxicology to explore the role and underlying mechanisms of an environmental pollutant in gastric cancer: A study of Diisononyl Phthalate
Year: 2026
Type: article
Abstract: Diisononyl phthalate (DINP), a widely used plasticizer, has raised increasing concerns regarding its carcinogenic potential, but its specific role in gastric cancer (GC) remains unclear. This study employed an integrated strategy combining computational toxicology, network toxicology, and multi‑omics analysis to investigate the molecular mechanisms linking DINP to GC. Toxicity prediction indicated significant carcinogenic potential for DINP. Network toxicology revealed that the shared hub genes between DINP and GC were significantly enriched in pathways critical for chemical carcinogenesis, immune-inflammation, and hormone signaling. A prognostic risk model based on four core genes (TTR, MAPK14, NTRK3, FAAH) moderately stratified GC patients in the TCGA‑STAD cohort. Single-cell RNA sequencing revealed specific MAPK14 upregulation within immune cells in the tumor microenvironment (TME). Furthermore, qRTPCR experiments independently confirmed the increased expression of MAPK14 in GC cell lines compared with normal gastric epithelial cells. In AGS cells, DINP showed minimal acute cytotoxicity (72 h IC₅₀ > 100 μM) but dose‑dependently induced MAPK14 at sub‑toxic levels (EC₅₀ ≈ 35 μM). Molecular docking suggested that DINP can potentially interact with key targets, especially MAPK14 and FAAH. Our findings suggest that DINP may promote GC development through interactions with core targets like MAPK14, highlighting its potential role as an environmental risk factor and a candidate biomarker.
Authors: Shuling Xiao, Junzuo Lin
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,650
OpenAlex ID: W7118424771