Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases

Abstract

Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China.Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes’ protein expression levels.Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC.Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.

A systematic study of traditional Chinese medicine treating hepatitis B virus-related hepatocellular carcinoma based on target-driven reverse network pharmacology

“…The most significantly enriched terms were closely related to cell differentiation, proliferation, and migration processes, which were strongly associated with cancer occurrence, development, and metastasis ( Sack et al., 2018 ). These enriched terms were also observed in previous HBV-related HCC literature ( Wang et al., 2017 ; Fan et al., 2017 ; Zhang et al., 2021 ). Two molecular function terms most significantly enriched were associated with DNA-binding transcription factor binding, which was also closely linked to cancer ( Bai et al., 2020 ).…”

Identifying a Three-Gene Signature and Associated Drugs for Hepatitis B Virus-Related Hepatocellular Carcinoma Using Comprehensive Bioinformatics Analysis

“…) is encoded by the BUB1B gene. It is an integral part of the spindle assembly checkpoint during mitosis and postpones the anaphase onset while guaranteeing appropriate chromosome segregation (Zhang et al 2021). BUB1B enhances HCC development by activating the mTORC1 pathway (Fu et al 2016).…”

Characteristics of Hepatitis B Virus Genotype and Sub-Genotype in Hepatocellular Cancer Patients in Vietnam

“…In addition, only HBV associated with the HCC sample was obtained; HBV mutations related to disease progression were not documented. These investigations, coupled with the findings in this study, will improve our understanding of the relationship between HBV genotypes and disease progression in Vietnam, which has highly prevalent HBV infection [ 28 , 29 ].…”