UHRF1 Could Be a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Hepatocellular Carcinoma

Danfeng Li,1,&ast; Binlie Chen,1,2,&ast; Yongming Zeng,1,&ast; Huaiming Wang1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Medical college, Shantou University, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaiming WangDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, 515041, People’s Republic of ChinaTel +86 13750417745Fax +86 0754-88259850Email 13750417745@163.comObjective: This study was performed to investigate the relationship among UHRF1 expression, its biological function and immune infiltration in human hepatocellular carcinoma (HCC).Methods: Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, and The Cancer Genome Atlas (TCGA) databases were used to analyze UHRF1 expression between HCC and normal tissues. Subsequently, GEPIA, TCGA-Portal, Kaplan–Meier Plotter, Protein Atlas and SurvExpress databases were utilized for survival analysis. UHRF1 co-expression genes were identified via the cBioPortal and LinkedOmics databases. Further, gene ontology (GO) analysis as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. Protein–protein interaction (PPI) networks was constructed by STRING database and Cytoscape 3.7.1. Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm were employed to assess the correlation between UHRF1 and tumor immune infiltrates on TCGA database. TIMER 2.0 database was used to explore the correlation of UHRF1 expression and immune infiltration level in HCC. Additionally, RT-qPCR was used to analyze the expression of UHRF1 and the relative genes in HCC cell lines.Results: Expression level of UHRF1 was upregulated in HCC tissues compared with paired normal tissues (P < 0.05 in GEPIA; P = 1.78E− 6 in Oncomine; and P < 0.0001 in TCGA). Its high expression was significantly related with a shorter overall survival in five databases (P < 0.05). Function enrichment analysis demonstrated that functions of UHRF1 concentrated in cell division process and cell cycle (P < 0.05). High UHRF1 expression exhibited dysregulated immune infiltration (ie, neutrophils, eosinophils, dendritic cells resting, macrophages M2, macrophages M0) and poor survival of high UHRF1 expression was tight correlated with immune infiltration status. Moreover, TP53 mutation can lead to high expression of UHRF1 (P = 4.2E− 10).Conclusion: UHRF1 might function as an oncogene via inducing dysregulated immune infiltration in HCC and was identified as a novel prognostic biomarker and potential therapeutic target for HCC.Keywords: UHRF1, biomarker, prognosis, immune infiltrates, HC