基于生物信息分析方法探究ADME基因在肝癌的表达及潜在调控机制

Identification of Expression and Potential Regulatory Mechanism of ADME Gene in Hepatocellular Carcinoma Based on Bioinformatics Analysis

目的基于生物信息学分析方法,了解肝癌状态下肝脏中与药物吸收、分布、代谢及排泄(ADME)相关的基因表达及调控情况。方法首先通过GEO数据获取240个肿瘤组织和193个正常组织的基因芯片数据,利用鉴定显著差异的ADME基因。并进一步使用JASPER数据库获取转录因子基因集,使用WGCNA分析转录因子与差异ADME基因调控关联性。结果与正常肝组织相比,肿瘤组织中有66个ADME基因表达水平发生显著改变,其中6个上调60个下调。通过构建WGCNA共表达网络,并对blue模块和turqu oise模块分析,其中SLC39A1、NAT2、CYP39A1和CYP1A2主要分布在blue模块,与转录因子CA T、VEZF1、FOS和CEBPG高度相关;SLC12A9和SLC25A39主要分布在turquoise模块,与转录因子IRF3、GMEB2、PRDM4、SOX13高度相关。结论我们通过生物信息学分析发现多个ADME基因在肝癌中患者中异常表达,并通过WGCNA分析发现与之表达高度相关转录因子,为肝癌组织中ADME基因异常表达及其调控研究提供理论基础。

OBJECTIVE To understand the gene expression and regulation related to drug absorption,distribution,metabolism and excretion(ADME)in hepatocellular carcinoma by bioinformatics analysis.METHODS Gene chip data of 240 tumor tissues and 193 normal tissues were obtained from the GEO data,and significant differences of ADME genes were identified by using the microarray data.The Jasper database was used to obtain transcription factors′gene,and WGCNA was used to analyze the correlation between transcription factors and differential ADME gene regulation.RESULTS Compared with normal liver tissues,the expression levels of 66 ADME genes in tumor tissue were significantly changed.Six ADME genes were induced and 60 genes were inhibited.The co-expression network was constructed and analyzed by WGCNA.SLC39 A1,NAT2,CYP39 A1 and CYP1 A2 were mainly distributed in the blue module,which were highly correlated with the transcription factors CAT,VEZF1,FOS and CEBPG;SLC12 A9 and SLC25 A39 are mainly distributed in turquoise module,and are highly correlated with transcription factors IRF3,GMEB2,PRDM4 and SOX13.CONCLUSION By the bioinformatics analysis,we found that the expressions of some ADME genes were significantly changed in liver cancer patients.Besides,we found highly related transcription factors by the WGCNA analysis.Our study may provide a theoretical basis for the study of the expression and regulation of ADME gene in the hepatocellular carcinoma.