An integrated network toxicology and multi-omics study identifies ENO1 as a candidate mediator in benzo[a]pyrene-related gastric cancer progression.

This study employed an integrative toxicogenomic and multi-omics prioritization approach, combined with preliminary in vitro validation, to identify candidate mediators of benzo [a]pyrene (BaP)-associated gastric cancer progression. A BaP-target-gastric cancer interaction network was constructed by integrating toxicogenomic databases with public transcriptomic datasets. Candidate genes were prioritized using differential expression analysis, network-based screening, LASSO regression, and exploratory artificial neural network modeling. Molecular docking was used to generate an in silico structural hypothesis for possible BaP-ENO1 protein-level interaction, while GO/KEGG enrichment and single-cell RNA sequencing characterized associated biological processes and cellular expression patterns. Integrated analyses prioritized ENO1 as the top BaP-associated candidate in gastric cancer. Single-cell analysis revealed elevated ENO1 expression in gastric cancer epithelial cells and tumor-associated macrophages. In vitro experiments demonstrated that BaP enhanced gastric cancer cell proliferation and migration, effects that were partially attenuated by ENO1 knockdown. Collectively, these findings position ENO1 as a candidate mediator of BaP-associated gastric cancer progression and provide preliminary support for further investigation of the BaP-ENO1 relationship. The study also offers a cross-platform framework for prioritizing candidate targets in environmentally linked cancers.