卵巢癌肿瘤微环境关键基因遴选及守正创新中药方预测  

Selection of key genes in microenvironment of ovarian cancer and prediction of innovative traditional Chinese medicine prescriptions for maintaining integrity

作　　者：杨志城 孙彩虹 李瑶瑶 叶亮 叶冠[1] YANG Zhicheng;SUN Caihong;LI Yaoyao;YE Liang;YE Guan(Institute of Traditional Chinese Medicine,Central Research Institute of Shanghai Pharmaceutical Group,Shanghai 201203,China;Institute of Chinese Traditional Medicines,Ningbo Drug Inspection Institute,Ningbo 315048,China;Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]上海医药集团中央研究院中药研究所,上海201203 [2]宁波市药品检验所中药室,浙江宁波315048 [3]中国药科大学中药学院,江苏南京211198

出　　处：《中草药》2024年第24期8499-8516,共18页Chinese Traditional and Herbal Drugs

基　　金：上海医药中药传承和创新平台能力建设(2020006)。

摘　　要：目的通过生物信息学技术遴选干预卵巢癌的关键基因并分析其临床价值,结合中医理论预测潜在治疗OV的守正创新中药组方并分析其作用机制。方法首先,从TCGA数据库下载卵巢癌活检基因表达数据,使用Estimate计算肿瘤微环境中基质得分(stromal score),以中位数为标准分为高、低评分2组,采用Limma包以|log2(fold change)|>2、P<0.05为标准筛选显著差异表达基因(differentially expressed genes,DEGs),通过ClusterProfiler包对DEGs进行基因本体(gene ontology,GO)功能和京都基因与基因百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。DEGs导入STRING数据库中进行蛋白互作网络分析,结果通过Cytoscape中插件MCODE、cytoHubba分析获取关键基因。其次,从生存分析、差异表达、免疫细胞浸润、基因集变异分析(gene set variation analysis,GSVA)评分等角度验证关键基因的临床价值。最后,将关键基因导入Coremine Medical数据库预测具有潜在治疗作用的创新中药组合,基于卵巢癌病机筛选核心中药用药模式及药味作为守正中药组合,整合2部分作为守正创新中药方,采用中药复方网络药理学的方法分析其作用机制。结果获取卵巢癌患者活检数据381例,以中位基质得分(-312.7420685)分为低(190例)、高(191例)2组,筛选得到DEGs 202个。GO富集分析显示DEGs主要干预体液免疫应答、补体激活、吞噬功能等生物过程;免疫球蛋白复合物、质膜组成、T细胞受体复合物等细胞组成;抗原结合、免疫球蛋白受体结合、整合素结合等分子功能。KEGG富集分析显示DEGs主要干预信号分子和相互作用、免疫系统、运输和分解代谢等功能信号通路。蛋白互作及MCODE、cytoHubba筛选得Ⅴ型胶原α1(collagen type V alpha 1,COL5A1)、纤维连接蛋白(fibronectin,FN1)、XⅠ型胶原α1(collagen typeⅪalpha1,COL11A1)、Ⅰ型胶原α2(collagen typeⅠalpha 2,COL1A2)、原纤蛋白1(fibrillin Objective Through bioinformatics methods,we aim to screen out the key genes involved in the intervention of ovarian cancer(OV)and analyze their clinical value.Furthermore,based on traditional Chinese medicine(TCM)theory,we predict potential therapeutic herbal formulas and investigate their underlying mechanisms.Methods Download OA biopsy gene expression data from the TCGA database,use Estimate to calculate the stromal score in the tumor microenvironment,and divide it into high and low score groups using the median as the standard.Use the Limma package to calculate|log2(fold change)|>2,P<0.05 was used as the standard to screen significantly differentially expressed genes(DEGs),and the DEGs were enriched using the ClusterProfiler package for gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.DEGs were imported into the STRING database for protein interaction analysis,and the results were imported into cytoscape using the plug-in MCODE and cytoHubba plug-ins to analyze and intersect to obtain key genes.The key genes’clinical value were verified from the perspectives of survival analysis,differential expression,immune cell infiltration,and gene set variation analysis(GSVA)scores.Key genes were introduced into the Coremine Medical database to predict innovative TCM combinations with potential therapeutic effects.Secondly,based on the pathogenesis of ovarian cancer,core TCM medication patterns and medicinal flavors were screened as a TCM combination.The two parts of the formula were integrated and the new formula was analyzed using the method of traditional Chinese medicine compound network pharmacology.mechanism of action.Results A total of 381 cases of OV patient biopsy data were downloaded,which were divided into two groups:low(190 cases)and high(191 cases)based on the median stromalscore(−312.7420685),202 DEGs were screened.GO enrichment analysis showed that DEGs mainly interfere with biological processes such as humoral immune response,complement a

关 键 词：卵巢癌 肿瘤微环境 生物信息学 生存分析 守正创新中药方 南木香 千层塔 茺蔚子 猫爪草 杜仲 肿节风 红娘子 预知子 堇菜 鹿角 川芎 甘草 半夏 黄芩 当归 熟地黄 桔梗 大黄 茯苓 

分 类 号：Q811.4[生物学—生物工程] TP18[自动化与计算机技术—控制理论与控制工程] R285[自动化与计算机技术—控制科学与工程]