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肝细胞癌中铜死亡标志物的筛选及化合物的预测

Screening of Copper Death Markers in Hepatocellular Carcinoma and Prediction of Compounds
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摘要 通过文献查阅铜死亡相关基因,使用STRING数据库对铜死亡相关基因产物进行PPI分析;使用R语言、Kaplan-Meier方法、THPA以及TIMER等数据库进行铜死亡相关基因与HCC相关的差异表达分析、ROC分析、临床的相关性分析、免疫浸润,最后将得到的铜死亡相关基因进行药物筛选和分子对接.结果显示,共筛选出4个与肝癌相关性较强的铜死亡相关基因,即DLAT、CDKN2A、GLS和MTF1,它们主要参与TCA循环、铂类耐药性、癌症中的碳代谢、丙酮酸代谢、糖酵解/糖异生等.4个基因与患者5年生存率相关性较大,与性别、淋巴结转移、肿瘤分期和免疫细胞密切相关,最后筛选出阿霉素、表没食子素没食子酸酯、曲格列酮、熊去氧胆酸等与上述蛋白结合能力较高的活性化合物. Copper death-related genes were reviewed in the literature,and PPI analysis of copper death-related gene products was performed using the STRING database.Differential expression analysis of copper death-related genes associated with HCC,ROC analysis,clinical correlation analysis,and immune infiltration were performed using the R language,the Kaplan-Meier method,the THPA,and TIMER databases,and finally,the obtained copper deathrelated genes for drug screening and molecular docking.The results showed that a total of 4copper death-related genes with strong relevance to hepatocellular carcinoma were screened,i.e.,DLAT,CDKN2A,GLS,and MTF1,which were mainly involved in the TCA cycle,platinum resistance,carbon metabolism,pyruvate metabolism,and glycolysis/glycolysis in cancer.The four genes were highly correlated with patients'5-year survival and closely related to gender,lymph node metastasis,tumor stage,and immune cells.Finally,active compounds such as adriamycin,epigallocatechin gallate,troglitazone,and ursodeoxycholic acid were screened for their high binding capacity to the above proteins.
作者 张楠楠 付朝举 张学武 李军 ZHANG Nannan;FU Chaoju;ZHANG Xuewu;LI Jun(Guizhou University of Traditional Chinese Medicine,School of Basic Medical Sciences,Guiyang 550025,China;Guizhou University of Traditional Chinese Medicine,School of Pharmacy,Guiyang 550025,China)
出处 《河南大学学报(自然科学版)》 CAS 2023年第6期706-717,共12页 Journal of Henan University:Natural Science
基金 贵州省卫生健康委科学技术基金(gzwkj2023-266) 贵州省科技厅自然科学项目(黔科合基础ZK-[2023]一般428)
关键词 肝细胞癌 铜死亡 分子对接 发病机制 hepatocellular carcinoma copper death molecular docking pathogenesis
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