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目的 旨在阐明邻苯二甲酸二（2-乙基己基）酯（DEHP）诱发胃癌的潜在分子机制并发掘关键作用靶点。方法 综合应用基因综合数据库胃癌数据库、网络毒理学、癌症基因组图谱胃癌转录组及单细胞测序等多源数据，基于加权基因共表达网络分析技术识别关键模块，联合机器学习算法筛选DEHP诱导胃癌的核心基因。利用分子对接模拟结合构象，并结合实时荧光定量聚合酶链反应（qPCR）验证关键基因的表达水平。结果 初步筛选出21个潜在靶点，通过机器学习最终确定了7个关键核心基因。分子对接结果证实DEHP与核心靶蛋白具有强亲和力。生存分析显示ANGPT2和IL-6与胃癌患者的预后显著相关（P<0.05）。单细胞测序数据分析表明ANGPT2高表达于恶性肿瘤细胞和肌成纤维细胞，而IL-6则富集于树突状细胞。qPCR结果证实，ANGPT2在胃癌细胞株中显著高表达。结论 DEHP暴露与胃癌发生存在分子关联，其机制涉及对7个关键靶点的调控，并潜在激活PI3K-Akt信号通路及重塑肿瘤微环境。IL-6与ANGPT2同时具有预后价值。
Abstract：Objective To explore the potential molecular mechanisms and key targets of di(2-ethylhexyl) phthalate(DEHP) induced gastric cancer through molecular networks. Methods This study integrated multi-source data including the gene expression omnibus gastric cancer database, network toxicology, The cancer genome atlas gastric cancer transcriptomics, and single-cell sequencing. Weighted gene co-expression network analysis was applied to identify key modules, and machine learning algorithms utilized to screen core genes associated with DEHP-induced gastric cancer. Molecular docking simulations and quantitative realtime polymerase chain reaction(qPCR) were employed to verify the binding modes of DEHP with target proteins and the expression levels of key genes. Results A total of 21 core genes were identified as potential targets for DEHP-induced gastric cancer. Machine learning further determined 7 key core genes. Molecular docking results confirmed that DEHP exhibits strong affinity for the proteins encoded by these core genes. Kaplan-Meier survival curves showed that angiopoietin 2(ANGPT2) and interleukin 6(IL-6) are significantly associated with the prognosis of gastric cancer patients(P < 0.05). Single-cell sequencing data analysis indicated that ANGPT2 is highly expressed in malignant tumor cells and myofibroblasts, while IL-6 is enriched in dendritic cells. qPCR experimental results confirmed that ANGPT2 is significantly upregulated in gastric cancer cell lines. Conclusion Exposure to DEHP exhibits a molecular association with gastric cancer development, with its mechanism involving the regulation of seven key targets and potentially activating the PI3 KAkt signaling pathway alongside tumour microenvironment remodelling. Both IL-6 and ANGPT2 possess prognostic value.
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基本信息:
DOI：10.13885/j.issn.2097-681X.M20252348
中图分类号:R735.2
引用信息:
[1]薛婷,李监文,姚昌瑜,等.通过分子网络探讨DEHP诱导胃癌的潜在机制[J].兰州大学学报(医学版),2026,52(08):47-56.DOI:10.13885/j.issn.2097-681X.M20252348.
基金信息:
甘肃省科学技术厅联合基金项目（25JRRA1259）; 兰州市科技计划项目（2025-2-25）
2026-05-15
2026-05-15
2026-05-15