菌物学报2026，Vol.45Issue(4)：95-115,21.DOI:10.13346/j.mycosystema.250351
基于网络毒理学与机器学习整合分析揭示赭曲霉毒素A诱导胃癌的关键生物标志物及其免疫调控机制
Integrated analysis of network toxicology,machine learning,and multi-dimensional bioinformatics reveals the toxicological mechanisms of ochratoxin A in gastric carcinogenesis
摘要
Abstract
Gastric cancer(GC)is a multifactorial malignancy closely linked to environmental risk factors.Ochratoxin A(OTA),a widely distributed mycotoxin,has been classified as a probable human carcinogen.This study systematically elucidates the molecular mechanisms underlying OTA-induced gastric carcinogenesis.For the first time,through an integrated approach combining network toxicology,machine learning,and Mendelian randomization analysis,four key pathogenic genes(ESR1,GSK3β,MET,and MMP2)were identified and validated.The research further clarifies how OTA disrupts hormone signaling,metabolic homeostasis,and the tumor immune microenvironment,thereby driving cancer development through multi-pathway synergy.Notably,GSK3β was genetically confirmed for the first time to have a causal relationship with gastric cancer.These gene markers play a central regulatory role in gastric carcinogenesis and demonstrate significant diagnostic potential,providing novel biomarkers and a theoretical foundation for risk prediction and targeted intervention in OTA-associated gastric cancer.关键词
赭曲霉毒素A/胃癌/网络毒理学/机器学习/分子对接/核心基因/肿瘤微环境Key words
ochratoxin A/gastric cancer/network toxicology/machine learning/molecular docking/core genes/tumor microenvironment引用本文复制引用
白薇,钱紫星,黄国栋,饶显俊,陈晓霄,杨洋,魏玮..基于网络毒理学与机器学习整合分析揭示赭曲霉毒素A诱导胃癌的关键生物标志物及其免疫调控机制[J].菌物学报,2026,45(4):95-115,21.基金项目
国家重点研发计划"中医药现代化"重点专项(2023YFC3503600) （2023YFC3503600）
中国中医科学院望京医院高水平中医医院建设项目-中医药临床循证研究专项(WJYY-XZKT-2023-06) This work was supported by the National Key Research and Development Program of China"Modernization of Traditional Chinese Medicine"Key Project(2023YFC3503600)and the Wangjing Hospital,China Academy of Chinese Medical Sciences High-level Traditional Chinese Medicine Hospital Construction Project-Traditional Chinese Medicine Clinical Evidence-based Research Project(WJYY-XZKT-2023-06). （WJYY-XZKT-2023-06）
