摘要
目的采用生物信息学方法,研究益气养阴方干预鼻咽癌(Nasopharyngeal Carcinoma,NPC)的分子机制,并构建风险模型,为NPC诊断、药物干预提供新方法。方法利用R语言并联合GEO、TCGA、MsigDB、TCMSP、TCMID、TCMIP、Pubchem、GeneCards、STRING多个数据库信息,首先对NPC芯片进行差异分析、GSEA富集分析及网络药理学分析,获取益气养阴方干预NPC自噬靶点;Lasso回归聚焦后,进行分子相关性分析及GO、KEGG富集分析;TCGA表达矩阵与HPA数据库初步验证分子靶点的差异表达情况;计算风险得分后,构建风险预测模型,并进行预后及生存验证;最后采用Pearson分析评估分子靶点的免疫浸润相关性。结果NPC有440个DEGs,其中106个高表达,334个低表达,主要富集于DNA复制、苯丙氨酸代谢、错配修复等KEGG通路,且与免疫相关;益气养阴方中多个有效组分可干预NPC自噬的分子靶点共13个;Lasso回归聚焦后,发现PTGS2、NTRK2、TYMS、TOP2A、PLAU、NQO1、F3分子靶点最显著;表达矩阵与免疫组化结果初步验证PTGS2、TYMS、TOP2A、PLAU在NPC中高表达;以分子靶点为核心要素,构建NPC的Nomogram风险预测模型,此模型C-index为0.616,AUC为0.718,Kaplan-Meier生存曲线的HR=2.09;免疫浸润结果构建了13个分子靶点与24种免疫细胞的相关性。结论本研究以生物信息学为手段,多数据库联合预测出益气养阴方干预NPC自噬的分子靶点,评估其分子靶点的差异表达、富集分析、预后生存、免疫浸润机制,为抗NPC药物研发提供理论依据,为中医药现代化提供了新思路。
Objective To use bioinformatics methods to study the molecular mechanism of Yiqi Yangyin Decoction in intervention of Nasopharyngeal Carcinoma(NPC),and to construct a risk model to provide new methods for NPC diagnosis and drug intervention.Method Use R language and integrate multiple database information of GEO,TCGA,MsigDB,TCMSP,TCMID,TCMIP,Pubchem,GeneCards,STRING,first perform differential analysis on NPC chip,GSEA enrichment analysis and network pharmacology analysis to obtain beneficial Qi Yangyin Recipe interferes with NPC autophagy targets;after Lasso regression focus,perform molecular correlation analysis and GO and KEGG enrichment analysis;TCGA expression matrix and HPA database initially verify the differential expression of molecular targets;construct after calculating the risk score Risk prediction model,and prognosis and survival verification;Finally,Pearson analysis is used to evaluate the correlation of immune infiltration of molecular targets.Results NPC has 440 DEGs,106 of which are highly expressed and 334 are low expressed.They are mainly enriched in KEGG pathways such as DNA replication,phenylalanine metabolism,mismatch repair,etc.,and are related to immunity;in Yiqi Yangyin Recipe There are 13 molecular targets with multiple effective components that can interfere with NPC autophagy;after Lasso′s return to focus,it was found that the molecular targets of PTGS2,NTRK2,TYMS,TOP2A,PLAU,NQO1,and F3 were the most significant;expression matrix and immunohistochemical results Preliminary verification is that PTGS2,TYMS,TOP2A,PLAU are highly expressed in NPC;with molecular targets as the core elements,a Nomogram risk prediction model of NPC is constructed.The C-index of this model is 0.616,AUC is 0.718,and the HR of Kaplan-Meier survival curve is HR=2.09;The result of immune infiltration constructs the correlation between 13 molecular targets and 24 immune cells.Conclusion This study uses bioinformatics as a means and multiple databases to predict the molecular targets of Yiqi Yangyin Recipe for intervention in NPC autophagy,and evaluate its differential expression,enrichment analysis,prognostic survival,and immune infiltration mechanisms.It provides a theoretical basis for the research and development of anti-NPC drugs and new ideas for the modernization of Chinese medicine.
作者
杨伟丽
王贤文
彭坷平
胡革
杨仁义
宾骥
马月湘
吴琪
卢帅
朱镇华
Yang Weili;Wang Xianwen;Peng Keping;Hu Ge;Yang Renyi;Bin Ji;Ma Yuexiang;Wu Qi;Lu Shuai;Zhu Zhenhua(The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410007,China;College of Integrated Traditional Chinese and Western Medicine,Hunan University of Traditional Chinese Medicine,Changsha 410007,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第2期730-740,共11页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金面上项目(81973914):lncRNAs调控鼻咽癌细胞生物力学机制影响其转移潜能及益气解毒方干预效应研究,负责人:王贤文
湖南省创新型省份建设专项科普专题(2021ZK4105):中医治未病理论指导下省内高发疾病鼻咽癌的防治科普研究及实施,负责人:杨伟丽
湖南省中医药防治眼耳鼻喉疾病湖南省重点实验室开放基金(2018YGC03):“鸣天鼓”按摩导引治疗仪的研发
关键词
益气养阴方
鼻咽癌
差异分析
免疫治疗
风险模型
中医药
Yiqi Yangyin recipe
Nasopharyngeal carcinoma
Difference analysis
Immunotherapy
Risk model
Traditional Chinese medicine