摘要
目的:探讨葛根素调控铁死亡干预肝细胞癌的作用机制.方法:通过网络药理学、生物信息学和分子对接等方法对葛根素-铁死亡-肝细胞癌共同作用靶点进行综合分析.结果:交集靶点为PTGS2、AKR1C3、JUN、PLIN2、ALB;其中有4个关键靶点(AKR1C3、ALB、PTGS2、JUN)能与葛根素结合,差异表达结果表明均有显著差异,进一步通过THPA验证在人类正常组织和癌症组织之间的表达结果具有一致性,临床相关性分析表明四者均有突出临床意义.生存分析曲线表明,10年生存预后分析中AKR1C3具有显著生存意义(P＜0.05),ALB、PTGS2、JUN生存意义较差(P＞0.05);ROC曲线显示AKR1 C3的预测能力有较高准确性(AUC=0.945,CI=0.922～0.968).免疫浸润分析可知,AKR1C3表达与巨噬细胞等细胞浸润呈正相关,而与CD4+T细胞负相关.结论:葛根素可能通过靶向作用于AKR1C3基因调控铁死亡干预肝细胞癌.
Abstract
In this study we investigated the effect of puerarin on hepatocellular carcinoma by regulating ferropto-sis.Network pharmacology,bioinformatics and molecular docking methods were used to comprehensively analyze the common targets of puerarin,ferroptosis and hepatocellular carcinoma.The intersection targets were PTGS2,AKRv1C3,JUN,PLIN2,and ALB.Among them,four key targets(AKR1C3,ALB,PTGS2,JUN)could bind to puerar-in,and the differential expression results showed that there were significant differences.THPA verification showed that the expression results in normal human tissues and in cancer tissues were consistent.Clinical correlation analy-sis showed that all four targets had outstanding clinical significance.Survival analysis curve showed that AKR1C3 had significant survival significance in the ten-year survival prognosis analysis(P＜0.05),while ALB,PTGS2 and JUN had poor survival significance(P＞0.05).The ROC curve showed that the predictive ability of AKR1C3 had high accuracy(AUC=0.945,CI=0.922-0.968).Immune infiltration analysis showed that AKR1C3 expression was positively correlated with the infiltration of macrophages and other cells,while negatively correlated with CD4+T cells.In conclusion,puerarin may regulate ferroptosis in hepatocellular carcinoma by targeting AKR1C3 gene.
NETL
NSTL
维普
万方数据