Author/Authors :
Alavian Seyed-Moayed نويسنده , Jazayeri Seyed Mohammad نويسنده Hepatitis B Molecular Laboratory-Department of Virology-School of Public Health-Tehran University of Medical Sciences, Tehran , Asghari Matin نويسنده Department of Agronomy and Plant Breeding, College of Agriculture and Natural Resources, University of Tehran, Karaj, I.R. Iran. , Poorebrahim Mansour نويسنده Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran. , Poortahmasebi Vahdat نويسنده Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran , Amiri Mehdi نويسنده Department of Cell Biology and Anatomy, Schulich School of Medicine and Dentistry, Western University, London, Canada , Salarian Ali نويسنده Department of Neuroscience and Addiction Studies, School
of Advanced Technologies in Medicine, Tehran University of Medical
Sciences, Tehran, IR Iran , Ataei Atousa نويسنده Institute of Fundamental Medicine and Biology, Kazan
Federal University, Kazan, Russia
Abstract :
Background The natural history of chronic hepatitis B (CHB)
infection is divided into different phases including immune tolerance
(IT), immune clearance (or immune active [IA]), inactive carrier (IC),
and reactivation. Despite utilizing high-throughput data, the distinct
immunological mechanisms of these phases have been insufficiently
investigated. Objectives The aim of the present study was to determine
candidate disease-associated genes and significantly altered biological
processes for each phase of CHB infection. Methods The gene expression
profiles of 83 CHB patients (22 IT, 50 IA, and 11 IC phases) were
obtained from gene expression omnibus (GEO dataset: GSE65359) and
analyzed by bioinformatics tools. Several plugins of Cytoscape software
were used to construct protein-protein interaction (PPI) networks and
measure their topological properties. Subsequently, functional
annotation and signaling pathway enrichment were carried out using the
database for annotation, visualization and integrated discovery (DAVID)
and Kyoto encyclopedia of genes and genomes (KEGG). Results 449 and 452
deregulated genes were identified in IT-IA and IA-IC patients,
respectively. Gene ontology and KEGG pathway analyses showed that
several immune response-associated genes and signaling pathways (i.e.
cytokine-cytokine receptor interaction, chemokine signaling pathway and
T cell receptor signalling pathway) were upregulated in the IA phase,
but downregulated in the IC phase. The LCK (encoding a tyrosine kinase)
was determined as the most important hub gene of both constructed PPI
networks. Furthermore, other immune response-associated genes such as
CXCR3, VCAN, MYC, and STAT1 were found to be the important hub genes in
clinical phases of CHB. Conclusions The immune response-related pathways
were found to be up and downregulated in the immune clearance phase and
inactive carrier phase of CHB, respectively. The LCK hub gene might help
the pathogenesis of different phases of CHB and serve as a therapeutic
target for the treatment of hepatitis B virus.
