首页|生物信息学分析端粒相关基因亲核素A2为肝细胞癌预后核心基因及中药预测

生物信息学分析端粒相关基因亲核素A2为肝细胞癌预后核心基因及中药预测

扫码查看
目的:探究端粒相关肝癌的差异基因,并预测其相关中药,以提供治疗肝癌端粒相关中医理论,为中医药现代化探索新途径.方法:下载并整理TCGA数据库中肝癌相关数据,以GEO数据库GSE14520数据集中242例肝癌患者的数据作为验证数据集,使用R语言中的DESeq2函数对其基因表达值进行差异分析,分别从GeneCards数据库、京都基因与基因组百科全书数据库、基因本体论数据库、NCBI数据库中检索端粒相关基因,运用R语言中的Glmnet函数将肝癌基因表达值进行最小绝对收缩和选择算子(Least Absolute ShrinKage and Selection Operator,LASSO)回归,进一步筛选预后关键基因.对上述三者基因集取交集,获取肝癌端粒相关核心基因,对核心基因进行生存、临床、富集分析等,以验证其可行性.通过CTD数据库和COREMINE数据库预测核心基因相关中药,对预测中药进行四气、五味、归经频次分析.结果:通过差异分析共获取4 547个肝癌差异基因,其中包含1 198个下调基因和3 349个上调基因;从各个基因数据库中共检索出2 173个端粒相关基因;LASSO回归分析中,从肝癌基因中共筛选出8个预后关键基因.取三者的交集,共获取到1个肝癌端粒相关核心基因亲核素A2(Karyopherin Alpha 2,KPNA2).单基因生存分析表明,KPNA2为肝癌患者不良预后表达基因,且受试者工作特征曲线结果较好;KPNA2基因表达与肿瘤分期也具有重要联系;通过GSEA富集分析验证,KPNA2具有端粒相关生物过程.KPNA2共映射出74味中药,四气以温、平、寒为主,五味以甘、辛、苦为主,归经多归肺经、肝经、脾经;按功效分类,多为补虚药、化痰药、活血化瘀药.结论:本研究揭示肝癌中的端粒相关基因及诊断标志物,并探讨相应中药用药规律,为肝癌的中医药临床治疗与新药研发提供新见解.
Bioinformatics analysis of telomere-associated gene KPNA2 as a prognostic core gene in hepatocellular carcinoma and prediction of Chinese medicine
Objective:To explore telomere-related liver cancer differential genes and predict their related Chinese medicines,so as to provide telomere-related TCM theories for the treatment of liver cancer patients,and explore new ways for the modemization of TCM.Methods:The liver cancer-related data in TCGA database was downloaded and sorted out.The data of 242 liver cancer patients from the GSE14520 data set in GEO database was used as the validation data set.The difference of gene expression values were analyzed by DESeq2 function in R language software.GeneCards database,KEGG database,GO database,and NCBI database were used to retrieve telomere-related genes.The LASSO regression of liver cancer gene expression values was performed by the Glmnet function in R language software to further screen for prognostic key genes.The intersection of the above three gene sets was taken to obtain the telomere-related core genes of hepatocellular carcinoma.The feasibility of the core genes was verified through survival analysis,clinical analysis,and enrichment analysis.The core gene-related Chinese medicines were predicted by CTD database and COREMINE database.The predicted Chinese medicines were analyzed based on the frequencies of medicinal properties,medicinal flavors,and the attributed meridians.Results:The differential analysis identified a total of 4 547 hepatocellular carcinoma differential genes,including 1 198 down-regulated genes and 3 349 up-regulated genes.A total of 2 173 telomere-associated genes were retrieved from various gene databases.Eight prognostic key genes were screened out from liver cancer genes through LASSO regression analysis.One hepatocellular carcinoma telomere-associated core gene,KPNA2,was obtained through the intersection of the three gene sets.The single-gene survival analysis showed that KPNA2 was a poor prognostic expression gene in hepatocellular carcinoma patients,and the ROC curve was better.The gene expression of KPNA2 was also significantly associated with tumor stage.KPNA2 was verified to have a telomere-associated bioprocess through GSEA enrichment analysis.A total of 74 Chinese medicines were mapped to KPNA2.The medicinal properties were mainly warm,moderate,and cold,and medicinal flavors were mainly sweet,pungency,and bitterness.The attributed meridians were mostly the lung meridian,liver meridian,and spleen meridian.According to the efficacy classification,most of them were medicines for tonifying,resolving phlegm,and promoting blood circulation and removing blood stasis.Conclusion:This study revealed telomere-related genes and diagnostic markers in hepatocellular carcinoma and explored the medication rule of corresponding Chinese medicines,so as to provide new insights for the clinical treatment of hepatocellular carcinoma in traditional Chinese medicine and the research and development of new medicines.

BioinformaticsHepatocellular carcinomaTelomereChinese medicine prediction

徐子皓、刘逸藩、程良斌

展开 >

湖北中医药大学,湖北 武汉,430061

湖北中医药大学附属湖北省中医院,湖北 武汉,430061

生物信息学 肝细胞癌 端粒 中药预测

2024

中医临床研究
中华中医药学会

中医临床研究

影响因子:0.839
ISSN:1674-7860
年,卷(期):2024.16(31)