生信分析二氢丹参酮Ⅰ抗基底样型乳腺癌机制

Bioinformatics analysis of the mechanism of dihydrotanshinoneⅠagainst basal-like breast cancer

[目的]探究二氢丹参酮Ⅰ抗基底样型乳腺癌(Basal-like breast cancer,BLBC)的机制。[方法]通过pharmmapper数据库反向垂钓二氢丹参酮I相关靶点;以“basal-like”为关键词,于TCGA数据库中下载临床BLBC的组学数据。使用Bioinformatics&Evolutionary Genomics数据库获取二者交集,并导入DAVID(v2021)数据库中进行KEGG注释和GO富集;另使用STRING(v11.5)数据库进行蛋白互作分析,并于Cytoscape(v3.8.1)软件中筛选核心基因。利用临床生信之家、Kaplan-Meier Plotter、UALCAN数据库验证核心基因的表达,获取预后生物标志物并分析其在不同表型乳腺癌及其它23种肿瘤中的表达水平。[结果]共获取二氢丹参酮Ⅰ相关靶点914个、BLBC相关靶点6394个。117个交集靶点共参与15条通路、109个GO条目。二氢丹参酮Ⅰ主要通过调节癌症的途径、细胞衰老、代谢途径等抗BLBC。Cytohubba所获10个核心基因中仅CCDK1的表达未通过大样本数据验证,且低表达的ZEB1与BLBC预后不良正相关,并在多种乳腺癌亚型中均显著低表达。[结论]二氢丹参酮Ⅰ通过调控包括ZEB1在内的多个靶点及通路治疗BLBC,其中低表达的ZEB1会造成BLBC患者生存和预后不良。

[Objective]To analyze the mechanism of dihydrotanshinoneⅠagainst basal-like breast cancer(BLBC).[Method]Reverse fishing for the targets of dihydrotanshinoneⅠthrough the pharmmapper database.Using“BLBC”as the keyword,the clinical BLBC omics data from the TCGA database was downloaded.The Bioinformatics&Evolutionary Genomics database was used to get the intersection of the two and import them into the DAVID(v2021)database for KEGG pathway annotation and GO enrichment analysis.The intersection targets were imported into the STRING(v11.5)database for interaction analysis,and the core genes were screened in the Cytoscape(v3.8.1)software.Assistant for Clinical Bioinformatics,Kaplan-Meier Plotter and UALCAN databases were used to verify the expression of core genes and obtain the prognostic biomarker,and its expression levels in different phenotypes of breast cancer and other 23 types cancers were analyzed.[Result]A total of 914 non-redundant dihydrotanshinoneⅠ-related targets and 6394 BLBC-related targets were obtained.Among them,117 intersection targets participated in 15 pathways and 109 GO entries.The enrichment results showed that dihydrotanshinoneⅠmainly treated BLBC by regulating cancer pathways,cell senescence,and metabolic pathways.Among the 10 core genes obtained by Cytohubba,only the expression of CCDK1 had not been verified by large sample data,and the low expression of ZEB1 was positively correlated with the poor prognosis of BLBC patients.And it was significantly down-regulated in various breast cancer subtypes.[Conclusion]DihydrotanshinoneⅠtreated BLBC by regulating the pathways involved in multiple targets including ZEB1,and the low expression of ZEB1 leaded to the poor survival and prognosis of BLBC patients.