PUS1 May Be a Potential Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S405621

Chenlu Lan, Xinlei Huang, Xiwen Liao, Xin Zhou, Kai Peng, Yongguang Wei, Chuangye Han, Tao Peng, Jianyao Wang, Guangzhi Zhu

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引用次数: 0

Abstract

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusion: PUS1 may be a prognostic biomarker and a underlying treatment target for HCC.

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PUS1可能是肝细胞癌的潜在预后生物标志物和治疗靶点。

目的:假尿嘧啶合酶(PUS)在肝细胞癌(HCC)中的作用机制尚不明确，本研究旨在探讨PUS基因在HCC中的作用。材料与方法:基于The Cancer Genome Atlas (TCGA)、International Cancer Genome Consortium (ICGC)和gene Expression Profiling Interactive Analysis (GEPIA)数据库，对PUS酶的差异表达及预后基因进行鉴定。对所鉴定的伪尿嘧啶合成酶1 (PUS1)基因进行进一步研究。采用Student’st检验分析PUS1的临床病理特征。采用Kaplan-Meier (KM)分析和Cox比例风险回归模型探讨预后意义。采用受试者工作特征(ROC)曲线评价诊断和预后价值。利用数据库注释、可视化和集成发现(DAVID)和基因集富集分析(GSEA)对PUS1的机制进行了研究。应用广西队列来验证差异表达。通过体外细胞实验研究了下调PUS1对肝癌细胞增殖、活性氧(ROS)水平、迁移和侵袭的影响。结果:PUS1在HCC组织中明显过表达，PUS1高表达的患者与临床病理特征不乐观相关。生存分析显示，PUS1高表达与较差的总生存期(OS)和1年无复发生存期(RFS)相关，是一个独立的危险因素。同时ROC曲线显示PUS1对HCC有诊断和预后意义。功能富集分析表明，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可显著抑制HCC细胞的迁移、增殖、侵袭，提高ROS水平。结论:PUS1可能是HCC的预后生物标志物和潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

3.30

自引率

5.30%

发文量

110

审稿时长

16 weeks

期刊介绍： Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.