基于生物信息学分析肺腺癌中铜死亡CDKN2A基因及潜在中药预测  

Bioinformatics Analysis of Cuproptosis-Related Gene CDKN2A and Prediction of Potential Traditional Chinese Medicine in Lung Adenocarcinoma

作　　者：李颖 谢飞宇 褚雪镭 蔡亚芳 薛鹏 朱世杰[2] LI Ying;XIE Feiyu;CHU Xuelei;CAI Yafang;XUE Peng;ZHU Shijie(Graduate School,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Oncology,Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]北京中医药大学研究生院,北京100029 [2]中国中医科学院望京医院肿瘤科,北京100102

出　　处：《辽宁中医杂志》2024年第6期1-4,I0001,I0002,共6页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973640)。

摘　　要：目的运用生物信息学分析铜死亡CDKN2A基因在肺腺癌中的表达水平、预后价值、免疫细胞浸润、相关基因筛选、功能富集分析及潜在中药预测,以期为临床治疗提供参考。方法使用GEPIA2和UALCAN,研究CDKN2A在肺腺癌患者中的表达情况,研究它与患者的年龄、性别和种族等之间存在的相关性;使用KM-plotter来评估预后价值;使用TIMER 2.0进行免疫浸润相关性分析;利用LinkedOmics数据库筛选相关基因,进行功能富集分析;利用COREMINE数据库进行中药预测,TCMSP数据库、HERB数据库及Swiss ADME平台筛选出上述中药有效活性成分,Cytoscape软件绘制“中药-活性成分”网络图。结果按照P<0.05检验水平,CDKN2A在肺腺癌组织中显著高表达,与患者吸烟、种族、TP53突变有关,与年龄、性别、肿瘤分级、肿瘤分期无关。CDKN2A高表达患者预后差(HR=1.73;P=0.00024)。CDKN2A与多种免疫细胞浸润相关。基因本体(gene ontology,GO)富集分析显示正相关基因主要参与细胞周期、ncRNA 3′-末端处理、核酸磷酸二酯键水解过程,表达于含细胞蛋白复合物、染色体组织,基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路分析显示正相关基因参与细胞周期与DNA复制过程。预测出虎刺、蜂房、兰花根(春兰根)等9味中药,其四气以温、平为主,五味以甘、辛、苦为主,归经主要归肝、肺、脾经,有效活性成分有73种。结论CDKN2A在肺腺癌组织中显著高表达,高表达患者预后差。虎刺、蜂房、兰花根等9味中药可能是治疗CDKN2A基因突变的肺腺癌患者的潜在药物。Objective Based on bioinformatics,analysis on the expression level,prognosis value,immune cell infiltration,related gene screening,functional enrichment analysisand prediction potential traditional Chinese medicine(TCM)of cuproptosis-related gene CDKN2A in lung adenocarcinoma was expected to provide reference for clinical treatment.Methods GEPIA2 and UALCAN were used to study the expression of CDKN2A in patients with lung adenocarcinoma,and study the correlation between CDKN2A gene and patients′age,gender,race and so on.The prognostic value was assessed by KM-plotter.Analysis of immune cell infiltration correlation was carried out by TIMER 2.0.The Linkedomics database was used to screen related genes of CDKN2A and functional enrichment analysis was performed.The COREMINE database was used to predict TCM,and the effective active ingredients of TCM were screened out by TCMSP database,HERB database and SwissADME tool.“TCM-active ingredients”network diagram was drawn by Cytoscape software.Results According to the level of P<0.05 testing level,CDKN2A was highly expressed significantly in lung adenocarcinoma tissue,which was related to patients′smoking,race,TP53 mutations and unrelated to age,tumor gender,tumor grade and tumor stage of patients.CDKN2A highly expressing patients had negative prognosis(HR=1.73;P=0.00024).CDKN2A was related to multiple immune cells.The gene ontology(GO)analysis showed that positive related genes mainly participate in the process of cell cycle,ncRNA 3′-end processing,nucleic acid phosphodiester bond hydrolysis and expressed in cellular protein-containing complex assembly and chromosome organization.Kyoto encyclopedia of genes and genomes KEGG pathway analysis showed that positive related genes participate in the process of cell cycle and DNA replication.Nine Chinese drugs,such as Huci(Indian Damnacanthus Herb),Fengfang(Honeycomb)and Lanhuagen(the root of Cymbidium goeringii),whose four Qi natures were mainly warm and flat,and the five tastes were mainly sweet,pungent and bitter.T

关 键 词：铜死亡 CDKN2A 肺腺癌 中药预测 生物信息学 

分 类 号：R273[医药卫生—中西医结合]