研究概要
本研究利用网络药理学和生物信息学识别EGCG与NPC之间的共享基因,旨在阐明EGCG抑制NPC的分子机制,并开发用于评估患者预后的预后模型。这些发现为抗NPC疗法的开发及其临床应用提供了潜在见解。
研究思路结论见上方概要
背景
表没食子儿茶素没食子酸酯(EGCG)是绿茶中研究较多的一种儿茶素,已被证明参与人鼻咽癌(NPC)细胞的抗增殖和凋亡。然而,EGCG 对抗 NPC 患者的药理靶点和机制仍有待详细研究。
方法
采用网络药理学和生物信息学方法探讨EGCG对NPC治疗作用的分子机制,重点开发预后风险模型并确定潜在治疗靶点。
结果
通过单因素Cox回归、LASSO回归和多因素Cox回归分析,开发了一种新的预后风险模型,纳入六个基因将患者分为低风险组和高风险组。Kaplan-Meier分析显示高风险组的无进展生存期显著缩短。该模型的准确性通过时间依赖性受试者工作特征(ROC)曲线进一步验证。ESTIMATE分析显示,与高风险组相比,低风险组的免疫评分、基质评分和总体ESTIMATE评分显著更高。免疫谱分析表明,两个风险组之间在五种免疫细胞亚型(记忆B细胞、调节性T细胞(Tregs)、γδT细胞、活化NK细胞和活化树突状细胞)上存在显著差异。此外,低风险组对常规化疗药物表现出更高的敏感性。免疫组织化学和分子对接分析确定CYCS和MYL12B是EGCG治疗的有前景的靶点。
展开英文摘要原文
BACKGROUND: Epigallocatechin gallate (EGCG), a frequently studied catechin in green tea, has been shown to be involved in the antiproliferation and apoptosis of human Nasopharyngeal carcinoma (NPC) cells. However, the pharmacological targets and mechanism by which EGCG can combat NPC patients remain to be studied in detail.
METHODS: Network pharmacology and bioinformatics were employed to investigate the molecular mechanisms underlying EGCG's therapeutic effects on NPC, with an emphasis on developing a prognostic risk model and identifying potential therapeutic targets.
RESULTS: A novel prognostic risk model was developed using univariate Cox regression, LASSO regression and multivariable Cox regression analyses, incorporating six genes to stratify patients into low- and highrisk groups. Kaplan-Meier analysis demonstrated significantly shorter progression-free survival in the high-risk group. The model's accuracy was further validated using time-dependent Receiver Operating Characteristic (ROC) curves. ESTIMATE analysis revealed significantly higher immune, stromal and overall ESTIMATE scores in the low-risk group compared to the high-risk group. Immune profiling indicated significant differences in five immune cell subtypes (memory B cells, regulatory T cells (Tregs), gamma delta T cells, activated NK cells and activated dendritic cells) between the two risk groups. Additionally, the low-risk group showed greater sensitivity to conventional chemotherapeutic agents. Immunohistochemistry and molecular docking analyses identified CYCS and MYL12B as promising targets for EGCG treatment.
CONCLUSION: This study utilised network pharmacology and bioinformatics to identify shared genes between EGCG and NPC, aiming to elucidate the molecular mechanisms through which EGCG inhibits NPC and to develop a prognostic model for assessing patient outcomes. The findings provide potential insights for the development of anti-NPC therapies and their clinical applications.
论文信息
- 作者
- Yang Y、Luo W、Feng Z、Chen X、Li J、Zuo L、Duan M、He X
- 第一作者单位
- Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China.China
- 通讯作者单位
- Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. lfx9911008@163.com.China
- 期刊
- Discover oncology2025 May 12