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

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

doi:10.2147/PGPM.S405621

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

Pharmgenomics Pers Med. 2023 Apr 15:16:337-355. doi: 10.2147/PGPM.S405621. eCollection 2023.

Authors

Chenlu Lan^#^{1

2}, Xinlei Huang^#^{1

2}, Xiwen Liao^{1

2}, Xin Zhou^{1

2}, Kai Peng^{1

2}, Yongguang Wei^{1

2}, Chuangye Han^{1

2}, Tao Peng^{1

2}, Jianyao Wang³, Guangzhi Zhu^{1

2}

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
² Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, People's Republic of China.
³ Department of General Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong Province, People's Republic of China.

^# Contributed equally.

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.

Keywords: HCC; PUS1; gene knockout; poor prognosis; pseudouridine synthase.

Grants and funding

Innovation Project of Guangxi Graduate Education (YCSW2022227, 02603222064X); Guangdong High-level Hospital Construction Fund (No. ynkt2021-zz07); Guangdong High-level Hospital Construction Fund; Shenzhen High-level Hospital Construction Fund; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education (grant nos. GKE2018-01, GKE2019-11 and GKE-ZZ202009); Natural Science Foundation of Shenzhen Science and Technology Innovation Commission (No. JCYJ20220530155610023); Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis (No. GXCDCKL201902).