scholarly journals Bioinformatic Identification and Validation of Key Genes and Biological Pathways Involved in Hepatitis B Virus-related Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Guan-Hua Ren ◽  
Fan-Biao Mei ◽  
Chao-Jun Zhang ◽  
Dong-Mei Cai ◽  
Long Long ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Key Genes

Abstract Objectives: Hepatocellular carcinoma (HCC) is a common malignant tumor severely scathing human health. As we all know, one of the main risk factors of HCC is chronic hepatitis B virus (HBV) infection, which involved in the oncogenesis of HCC through direct and indirect mechanisms such as inflammatory injury, integration into the host genome and interaction with some special target genes. This study aimed to identify these key genes potentially associated with HBV-related HCC by bioinformatics analyses.Results: Total of 320 DEGs was identified between HBV-related HCC tissue samples and adjacent normal samples. These DGEs were strongly associated with several biological processes, such as retinol metabolism and steroid hormone biosynthesis. A PPI network was constructed and top six hub genes, including CDK1, CCNB1, CDC20, CDKN3, HMMR and MKI67, were determined. GEPIA online tool analysis validated the six key hub genes had the same expression trend as predicted in The Cancer Genome Atlas (TCGA) datasets. The overall survival and disease-free survival reflected that high expression of CDK1, CDC20, HMMR, MKI67 and CCNB1 significantly predicted poor prognosis, whereas CDKN3 expression has no statistical differences in overall survival.Conclusion: The present study identified key genes and pathways involved in HBV-related HCC, which will improve our understanding of the mechanisms underlying the development and recurrence of HCC. The six identified genes might be potential biomarkers for the diagnosis and treatment of HBV-related HCC.

scholarly journals RAD50 predicts the prognosis of hepatitis B virus-related hepatocellular carcinoma

2020 ◽  
Author(s):  
Wangrui Liu ◽  
Wenhao Xu ◽  
Yuyan Chen ◽  
Liugen Gu ◽  
Xiaolei Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Differential Expression ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Partial Likelihood ◽  
Cox Regression Analysis ◽  
B Virus

Abstract Background Increasing evidence indicates that RAD50, which is involved in the DNA double-strand break (DSB) repair process, is also involved in cancer outcomes. However, its role in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) remains unclear.Aim This study was designed to investigate the expression of RAD50 and its prognostic value in HCC patients.Method A total of 207 patientswith HBV-associated HCCfrom two cohorts (107 and 100 patientsfrom the Affiliated Hospital of Youjiang Medical University of Nationalities and the Affiliated Hospital of Nantong University, respectively) were enrolled in the current study.The distribution of the categorical clinical-pathological data and the levels of RAD50 expression were compared with a χ 2 test. IHC staining of RAD50 was performed.A partial likelihood test based onunivariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS). The Oncomine online database was used to analyse and validate the differential expression of RAD50. The Kaplan-Meier method and a log-rank test were performed to assess the influence of RAD50 on survival at different levels.Results RAD50 was highly expressed in HCC tissues compared to normal tissues and was significantly correlated with OS in the TCGA cohort. The validation analysis indicated that significantly increased levels of RAD50 were expressed in HCC tissues in the two independent cohorts, AHYMUN and AHNTU. In addition, HCC patients with elevated RAD50 expression levels showed poor OS and DFSin the AHYMUN cohort and decreased OS and DF Sin the AHNTU cohort. Furthermore, four datasets obtained from the Oncomine database validated the analysis of the differential expression of RAD50 in HCC tumours and normal tissues.Discussion In our study, we demonstrated that RAD50 was positively correlated with poor prognosis in HCC patients in the TCGA cohort. Our study also suggested that increased RAD50 expression in HBV-related HCC is a marker of poor prognosis. In this study, the analysis of the data form the two cohorts supported our hypothesis and clearly demonstrated thehigh expression of RAD50 in tumour tissues from HCC patients, which results inincreases in the HCC recurrence rate and poor overall survival.

scholarly journals Creation of a Six-fingered Artificial Transcription Factor That Represses the Hepatitis B Virus HBx Gene Integrated into a Human Hepatocellular Carcinoma Cell Line

2012 ◽  
Vol 18 (4) ◽  
pp. 378-387 ◽  
Author(s):  
Xinghui Zhao ◽  
Zhanzhong Zhao ◽  
Junwei Guo ◽  
Peitang Huang ◽  
Xudong Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Hbv Infection ◽  
Luciferase Reporter ◽  
Artificial Transcription Factor ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.

Discovery of novel hepatitis B virus (HBV) antivirals and analysis of mechanisms of action of HBV-targeting agents

2017 ◽  
Author(s):  
◽  
Andrew Douglas Huber
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Treatment Options ◽  
Mechanisms Of Action ◽  
Hbv Infection ◽  
Viral Inhibition ◽  
University Of Missouri ◽  
Chronic Hepatitis B Virus ◽  
B Virus

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.

Age at First Establishment of Chronic Hepatitis B Virus Infection and Hepatocellular Carcinoma Risk

1992 ◽  
Vol 136 (9) ◽  
pp. 1115-1121 ◽  
Author(s):  
Chung-Cheng Hsieh ◽  
Anastasia Tzonou ◽  
Xenophon Zavitsanos ◽  
Evagelia Kaklamani ◽  
Shou-Jen Lan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Virus Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Carcinoma Risk

scholarly journals Screening and Functional Prediction of Key Candidate Genes in Hepatitis B Virus-Associated Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xia Chen ◽  
Ling Liao ◽  
Yuwei Li ◽  
Hengliu Huang ◽  
Qing Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Metabolic Process ◽  
Hub Genes ◽  
Kegg Pathway Analysis ◽  
B Virus

Background. The molecular mechanism by which hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) is still unknown. The genomic expression profile and bioinformatics methods were used to investigate the potential pathogenesis and therapeutic targets for HBV-associated HCC (HBV-HCC). Methods. The microarray dataset GSE55092 was downloaded from the Gene Expression Omnibus (GEO) database. The data was analyzed by the bioinformatics software to find differentially expressed genes (DEGs). Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, ingenuity pathway analysis (IPA), and protein-protein interaction (PPI) network analysis were then performed on DEGs. The hub genes were identified using Centiscape2.2 and Molecular Complex Detection (MCODE) in the Cytoscape software (Cytoscape_v3.7.2). The survival data of these hub genes was downloaded from the Gene Expression Profiling Interactive Analysis (GEPIA). Results. A total of 2264 mRNA transcripts were differentially expressed, including 764 upregulated and 1500 downregulated in tumor tissues. GO analysis revealed that these DEGs were related to the small-molecule metabolic process, xenobiotic metabolic process, and cellular nitrogen compound metabolic process. KEGG pathway analysis revealed that metabolic pathways, complement and coagulation cascades, and chemical carcinogenesis were involved. Diseases and biofunctions showed that DEGs were mainly associated with the following diseases or biological function abnormalities: cancer, organismal injury and abnormalities, gastrointestinal disease, and hepatic system disease. The top 10 upstream regulators were predicted to be activated or inhibited by Z-score and identified 25 networks. The 10 genes with the highest degree of connectivity were defined as the hub genes. Cox regression revealed that all the 10 genes (CDC20, BUB1B, KIF11, TTK, EZH2, ZWINT, NDC80, TPX2, MELK, and KIF20A) were related to the overall survival. Conclusion. Our study provided a registry of genes that play important roles in regulating the development of HBV-HCC, assisting us in understanding the molecular mechanisms that underlie the carcinogenesis and progression of HCC.

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