ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Integrated network toxicology, machine learning algorithms and TMT proteomics reveal the mechanism of 18β glycyrrhetinic acid against gastric cancer
Provisionally accepted
- Ningxia Medical University, Yinchuan, China
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The purpose of this paper is to explore the mechanism of 18β glycyrrhetinic acid (18β-GRA) in treating gastric cancer. Firstly, the toxicological effects of 18β-GRA were predicted using the ProTox3.0 database. Then, candidate biomarkers for the anti-gastric cancer of 18β-GRA were screened using the weighted gene co-expression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), the support vector machine (SVM), the random forest algorithm combined with the TMT proteomics methods. Additionally, we explored the potential upstream transcription factors and downstream interacting proteins of the biomarkers. The WGCNA method yielded 269 targets, while TMT proteomics analysis identified 6,273 genes. Among these, 12 targets were identical. Using LASSO, SVM, and random forest algorithms, three candidate markers were identified: insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), keratin 6B (KRT6B), and E3 ubiquitin-protein ligase NEDD4-like (NEDD4L). Based on molecular docking and molecular dynamics results, NEDD4L is believed to be a 18β-GRA biomarker, while sodium channel protein type 5 subunit alpha (SCN5A) and early growth response protein 1 (EGR1) are the potential upstream and downstream regulatory proteins, respectively. These findings provide a theoretical basis for future experimental verification.
Keywords: 18β glycyrrhetinic acid, TMT proteomics, machine learning algorithms, NEDD4L, gastric cancer
Received: 10 Sep 2025; Accepted: 12 Dec 2025.
Copyright: © 2025 Lu, Jia, Li, Wang, Ye, Wenjing, Zhang, Yuan and Nan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yi Nan
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