葛花解酲方作用于CCL2、BIRC5调控自噬治疗肝细胞癌的研究

Gehua Jiecheng decoction acts on CCL2 and BIRC5 to regulate autophagy in the treatment of hepatocellular carcinoma

为探讨葛花解酲方(GHJCF)通过调控自噬干预肝细胞癌进展的作用机制,根据GEO数据库中GSE45267和GSE87630肝癌数据集,将自噬相关的222个基因与GHJCF靶点和数据集的差异表达基因用韦恩图取交集得出关键基因,进行靶点预测并建立蛋白质-蛋白质相互作用网络图;随后利用生物信息学的方法进行临床因素相关分析和生存预后分析。最后使用分子对接进而筛选出GHJCF通过调控自噬干预肝细胞癌进展的作用机制,获得4个GHJCF介导自噬干预肝细胞癌的靶点。与对照组(癌旁组织)相比,肝癌组中CCL2、NFE2L2、FAS和BIRC5表达均具有显著差异;THPA数据库病理切片验证NFE2L2、CCL2、BIRC5等蛋白在正常组中低表达,在癌症组织中高表达;CCL2和BIRC5与性别、癌症分期、淋巴结转移具有显著相关性;5年生存预后分析显示两者都有预后价值;最后分子对接显示BIRC5蛋白能与GHJCF中的染料木素、槲皮素、葛根素和木犀草素成分结合且对接分数较高,CCL2能与槲皮素成分结合且对接分数较高。通过以上生物信息学分析,结合临床数据相关性,GHJCF可能通过染料木素、槲皮素、葛根素和木犀草素作用于BIRC5、CCL2,调节HCC的自噬,进而对HCC有抑制作用。

To investigate the mechanism of action of Gehua Jiecheng decoction(GHJCF)in interfering with hepatocellular carcinoma progression by regulating autophagy.Based on the GSE45267 and GSE87630 hepatocellular carcinoma datasets in the GEO database,222 genes associated with autophagy were intersected with GHJCF targets and differentially expressed genes from the dataset using Venn diagrams to derive key genes for target prediction and to establish protein-protein interaction network's diagram;subsequently,clinical factor correlation analysis and survival prognosis analysis were performed using the bioinformatics approach.Finally,molecular docking was used to then screen the mechanism of action of GHJCF to intervene in hepatocellular carcinoma progression through regulation of autophagy.Four GHJCF-mediated targets of autophagy intervention in hepatocellular carcinoma were obtained.The expression of CCL2,NFE2L2,FAS and BIRC5 were significantly different in the hepatocellular carcinoma group compared with the control group(paraneoplastic tissue);THPA database pathological sections verified that NFE2L2,CCL2 and BIRC5 proteins were lowly expressed in the normal group and highly expressed in the cancer tissue;CCL2 and BIRC5 were significantly associated with gender,cancer stage and lymph node metastasis The 5-year survival prognosis analysis showed that both proteins had prognostic value;finally,molecular docking showed that BIRC5 protein could bind to the genistein,quercetin,geranin and lignan components in GHJCF with higher docking fraction,and CCL2 could bind to the quercetin component with higher docking fraction.Through the above bioinformatics analysis,combined with the correlation of clinical data,GHJCF may act on BIRC5,CCL2 through genistein,quercetin,geranin and lignan to regulate the autophagy of HCC,and thus have an inhibitory effect on HCC.