Identification of Potential Hub Genes Related to Diagnosis and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma via Integrated Bioinformatics Analysis

Author:

Tang Yuqin12,Zhang Yongqiang34ORCID,Hu Xun2ORCID

Affiliation:

1. School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

2. Biorepository, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China

3. Molecular Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China

4. West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610041, China

Abstract

Hepatocellular carcinoma (HCC) is a common malignant cancer with poor survival outcomes, and hepatitis B virus (HBV) infection is most likely to contribute to HCC. But the molecular mechanism remains obscure. Our study intended to identify the candidate potential hub genes associated with the carcinogenesis of HBV-related HCC (HBV-HCC), which may be helpful in developing novel tumor biomarkers for potential targeted therapies. Four transcriptome datasets (GSE84402, GSE25097, GSE94660, and GSE121248) were used to screen the 309 overlapping differentially expressed genes (DEGs), including 100 upregulated genes and 209 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to explore the biological function of DEGs. A PPI network based on the STRING database was constructed and visualized by the Cytoscape software, consisting of 209 nodes and 1676 edges. Then, we recognized 17 hub genes by CytoHubba plugin, which were further validated on additional three datasets (GSE14520, TCGA-LIHC, and ICGC-LIRI-JP). The diagnostic effectiveness of hub genes was assessed with receiver operating characteristic (ROC) analysis, and all hub genes displayed good performance in discriminating TNM stage I patient samples and normal tissue ones. For prognostic analysis, two prognostic key genes (TOP2A and KIF11) out of the 17 hub genes were screened and used to develop a prognostic signature, which showed good potential for overall survival (OS) stratification of HBV-HCC patients. Gene Set Enrichment Analysis (GSEA) was performed in order to better understand the function of this prognostic gene signature. Finally, the miRNA–mRNA regulatory relationships of all hub genes in human liver were predicted using miRNet. In conclusion, the current study gives further insight on the pathogenesis and carcinogenesis of HBV-HCC, and the identified DEGs provide a promising direction for improving the diagnostic, prognostic, and therapeutic outcomes of HBV-HCC.

Funder

Research Project of a Pilot Study on Establishing Natural Population Cohorts in Western China

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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