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Updated: Aug 5, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
From Food Contaminant to Therapeutic Target: Identification of KCNE2 and 5-Azacytidine for Gastric Cancer via
Meimei Chen1,2, Shaohua Zheng3, Tingjian Wu1,2
1College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Abstract:
Background: Benzo[a]pyrene (BaP), a common food contaminant, is a recognized gastric carcinogen. This study aimed to identify therapeutic targets and repurposed drugs for gastric cancer (GC) using BaP as a network toxicology query. Methods: An integrated strategy combining network toxicology, multi-omics, machine learning (Random Forest, LASSO, SVM-RFE), and experimental validation was applied. Results: By intersecting GC-associated genes with BaP-related targets and machine learning, we identified three hub genes. The logistic regression model further revealed KCNE2 as a protective factor (OR = 0.515, 95% CI: 0.383-0.692), while SULF1 (OR = 2.940, 95% CI: 1.399-6.179) and TIMP1 (OR = 5.351, 95% CI: 2.020-16.743) were identified as potential risk factors. Survival analysis confirmed their prognostic significance. Single-cell transcriptomics descriptively showed TIMP1 and SULF1 enrichment in malignant/stromal cells and fibroblasts, respectively, whereas KCNE2 was restricted to normal epithelial cells and silenced in tumors. GSVA implicated epigenetic regulation, ECM remodeling, and TGF-β signaling. Molecular docking and dynamics simulations suggested that BaP can form stable complexes with DNMT1 and DNMT3A. Accordingly, drug enrichment analysis identified DNMT inhibitor 5-azacytidine as a top candidate. Cellular experiments confirmed that 5-azacytidine selectively inhibited GC cells and was associated with modulation of the DNMT3A-KCNE2 axis. Conclusions: Our findings provide a novel molecular target and a repurposed drug for GC from the perspective of a food contaminant.
Insights
This study identifies novel therapeutic targets and a repurposed drug for gastric cancer (GC) by investigating the food contaminant benzo[a]pyrene (BaP). We found 5-azacytidine effectively inhibits GC cells by modulating the DNMT3A-KCNE2 axis.
Area of Science:
- Oncology
- Toxicology
- Bioinformatics
Background:
- Benzo[a]pyrene (BaP), a prevalent food contaminant, is a known gastric carcinogen.
- Gastric cancer (GC) remains a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To identify potential therapeutic targets for gastric cancer (GC) using network toxicology.
- To discover repurposed drugs for GC treatment by leveraging BaP as a molecular probe.
- To elucidate the molecular mechanisms underlying BaP-induced gastric carcinogenesis.
Main Methods:
- Integrated network toxicology, multi-omics data, and machine learning (Random Forest, LASSO, SVM-RFE).
- Applied logistic regression, survival analysis, and single-cell transcriptomics for gene significance.
- Utilized molecular docking, dynamics simulations, and cellular experiments for drug validation.
Main Results:
- Identified three hub genes: KCNE2 (protective), SULF1, and TIMP1 (risk factors) with prognostic significance in GC.
- Discovered BaP interaction with DNMT1 and DNMT3A, implicating epigenetic dysregulation.
- 5-azacytidine, a DNMT inhibitor, selectively inhibited GC cells via the DNMT3A-KCNE2 axis.
Conclusions:
- Novel therapeutic targets (KCNE2, SULF1, TIMP1) and a repurposed drug (5-azacytidine) for GC were identified.
- The study provides a unique perspective on GC treatment strategies informed by food contaminant toxicology.
- Findings highlight the potential of targeting epigenetic regulators in GC therapy.
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