■假尿苷合酶(PUS)在肝细胞癌(HCC)中的作用机制尚不明确,本研究的目的是探讨PUS基因在HCC中的作用。
■根据癌症基因组图谱(TCGA)鉴定了PUS酶的差异表达和预后基因,国际癌症基因组联盟(ICGC)和基因表达谱交互式分析(GEPIA)数据库。对于确定的基因,假尿苷合酶1(PUS1),用于进一步研究。采用t检验分析PUS1的临床病理特征。通过Kaplan-Meier(KM)分析和Cox比例风险回归模型探索预后意义。应用受试者工作特征(ROC)曲线评价诊断和预后价值。注释数据库,可视化,综合发现(DAVID)和基因集富集分析(GSEA),以探索PUS1的机制。应用广西队列验证差异表达。进行了体外细胞实验以研究对增殖的影响,活性氧(ROS)水平,迁移,敲低PUS1后肝癌细胞的侵袭。
■PUS1在HCC组织中显著过表达,高PUS1患者的临床病理特征不理想。生存分析显示,高PUS1表达与低总生存率(OS)和1年无复发生存率(RFS)相关。是一个独立的危险因素。同时,ROC曲线显示PUS1对HCC具有诊断和预后意义。功能富集分析提示PUS1可能参与代谢途径,线粒体功能,非酒精性脂肪性肝病(NAFLD),和一些重要的致癌途径。细胞实验显示,敲低PUS1显著限制了迁移,扩散,侵袭能力和提高肝癌细胞的ROS水平。
■PUS1可能是HCC的预后生物标志物和潜在治疗靶标。
UNASSIGNED: The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC.
UNASSIGNED: Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 (PUS1), was used for further research. The clinicopathological feature of PUS1 was analyzed by Student\'s t-test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of PUS1. A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of PUS1.
UNASSIGNED: PUS1 was significantly overexpressed in HCC tissues, and patients with high PUS1 were related to unpromising clinicopathological features. Survival analysis revealed high PUS1 expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that PUS1 had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that PUS1 may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of PUS1 significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells.
UNASSIGNED: PUS1 may be a prognostic biomarker and a underlying treatment target for HCC.