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An integrated network toxicology and multi-omics study identifies ENO1 as a candidate mediator in

Haixia Liu1, Binru Di1, Xiaoding Men1

  • 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Frontiers in Pharmacology
|July 14, 2026
PubMed

Insights

Benzo[a]pyrene (BaP) exposure may drive gastric cancer. Researchers identified ENO1 as a key mediator, finding that blocking ENO1 reduced cancer cell growth and migration in preliminary tests.

Area of Science:

  • Environmental Health
  • Cancer Biology
  • Genomics

Background:

  • Benzo[a]pyrene (BaP) is an environmental carcinogen linked to various cancers.
  • Gastric cancer progression mechanisms, particularly those influenced by environmental factors, require further elucidation.
  • Identifying specific molecular mediators is crucial for understanding and potentially intervening in BaP-associated gastric cancer.

Purpose of the Study:

  • To identify candidate genes mediating benzo[a]pyrene (BaP)-associated gastric cancer progression.
  • To construct and analyze a BaP-target-gastric cancer interaction network.
  • To validate candidate mediators using multi-omics and in vitro approaches.

Main Methods:

  • Integrative toxicogenomic and multi-omics data analysis.
  • Network construction and analysis (differential expression, LASSO regression, artificial neural networks).
  • In silico molecular docking, gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, single-cell RNA sequencing, and in vitro validation.

Main Results:

  • Enolase 1 (ENO1) was prioritized as the top BaP-associated candidate gene in gastric cancer.
  • Elevated ENO1 expression was observed in gastric cancer epithelial cells and tumor-associated macrophages.
  • In vitro studies showed BaP increased gastric cancer cell proliferation and migration, partially reversed by ENO1 knockdown.

Conclusions:

  • Enolase 1 (ENO1) is a potential mediator of benzo[a]pyrene (BaP)-associated gastric cancer progression.
  • The findings support further investigation into the BaP-ENO1 relationship in gastric cancer.
  • The study presents a framework for prioritizing environmental exposure-linked cancer targets.
Keywords:
alpha-enolase (ENO1)benzo[a]pyrenegastric cancermachine learningnetwork toxicologytumor microenvironment

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