肝组织特异性基因IGFALS、CYP3A4、SLC22A1和CYP2E1可能与肝癌预后不良相关

目的 探索肝癌相关基因在肝癌发生发展过程中的功能和作用机制,以及关键基因作为肝癌潜在生物标志物及预后指标的可能。方法 从GEO数据库选择GSE57957、GSE121248、GSE36376和GSE14520 4个数据集,以P<0.05及|log₂FC|>1为标准使用GEO2R在线工具和VENN图软件筛选出4个数据集的共同显著差异表达基因(DEGs),通过Cytoscape3.6.1插件CytoHubba及分子复合物检测插件(MCODE)对DEGs之间联系密切程度进行分析筛选。通过基因表达谱交互式分析(GEPIA)对以P<0.05及|log₂FC|>2的显著DEGs进行生存分析,采用人类蛋白质图谱(HPA)检查正常肝脏组织和肝癌组织中关键基因的蛋白质表达。结果 筛选出在4个数据集中都明显上调基因45个,下调基因132个,MCODE有13个模块结果。以P<0.05及|log₂FC|>2进一步筛选出显著差异表达32个上下调基因,其中IGFALS、HGFAC、CYP3A4、SLC22A1、TAT和CYP2E1基因在肝脏组织中的表达量明显高于其他器官,HPA的免疫组织化学数据库显示,肝癌组织中的IGFALS、CYP3A4、SLC22A1和CYP2E1表达均明显下调,且与患者的低总存活率相关。结论 肝组织特异性基因IGFALS、CYP3A4、SLC22A1和CYP2E1在肝癌中低表达,且与不良预后相关,可能是肝癌潜在的生物标志物及预后指标。

Liver Tissue-specific Genes IGFALS,CYP3A4,SLC22A1 and CYP2E1 May be Associated with Poor Prognosis of Liver Cancer

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With P<0.05 and |log₂FC|>1 as the thresholds, we used GEO2R and Venn Diagram Software to filter out the common significant differentially expressed genes(DEGs).Cytoscape 3.6.1 plug-ins CytoHubba and molecular complex detection(MCODE)were used to screen out the hub genes and modules of DEGs.In addition, survival analysis of DEGs was performed by gene expression profiling(GEPIA), and Human Protein Atlas(HPA)were used to examine the protein expression levels of key genes in normal liver tissue and liver cancer tissue.Results There were 45 obviously up-regulated genes and 132 down-regulated genes, and MCODE identified 13 clusters.The cluster 1 and cluster 2 with higher scores included 16 genes and 13 genes, respectively.Among the 32 significant DEGs, IGFALS, HGFAC, CYP3A4, SLC22A1, TAT and CYP2E1 demonstrated significantly higher expression levels in liver tissue than in other organs.The HPA immunohistochemistry(IHC)data showed that the expression levels of IGFALS, CYP3A4, SLC22A1 and CYP2E1 in liver cancer tissue were significantly down-regulated and related to the low overall survival rate of patients.Conclusion The liver tissue-specific genes IGFALS, CYP3A4, SLC22A1 and CYP2E1 are under-expressed in liver cancer and associated with poor prognosis, which may be potential biomarkers and prognostic indicators for liver cancer.