Identification of Hub Genes and Potential Molecular Mechanisms in Patients with HBV-Associated Acute Liver Failure

Author:

Sun Ying1,Yu Haitao2,Li Fangfang3,Lan Liqiang4,He Daxin5,Zhao Haijun6,Qi Dachuan7ORCID

Affiliation:

1. Department of Gastroenterology, Qingdao Eighth People’s Hospital, Qingdao, China

2. Intensive Care Unit, Qingdao Municipal Hospital, Qingdao, China

3. Department of Respiratory Medicine, Qingdao Eighth People’s Hospital, Qingdao, China

4. Department of Endocrinology, Qingdao Eighth People’s Hospital, Qingdao, China

5. Department of Ultrasound, Qingdao Municipal Hospital, Qingdao, China

6. Department of Urology, Qingdao Municipal Hospital, Qingdao, China

7. Department of Surgery, Shanghai Fourth People’s Hospital Affiliated to Tongji University, Shanghai, China

Abstract

Hepatitis B virus (HBV) infection is a major cause of acute liver failure (ALF) in China, and mortality rates are high among patients who do not receive a matched liver transplant. This study aimed to determine potential mechanisms involved in HBV-ALF pathogenesis. Gene expression profiles under access numbers GSE38941 and GSE14668 were downloaded from the Gene Expression Omnibus database, including cohorts of HBV-ALF liver tissue and normal samples. Differentially expressed genes (DEGs) with false discovery rates (FDR) <0.05 and |log2(fold change)| >1 as thresholds were screened using the Limma package. Gene modules associated with stable disease were mined using weighed gene co-expression network analysis (WGCNA). A co-expression network was constructed and DEGs were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A gene-based network was constructed to explore major factors associated with disease progression. We identified 2238 overlapping DEGs as crucial gene cohorts in ALF development. Based on a WGCNA algorithm, 10 modules (modules 1-10) were obtained that ranged from 75 to 1078 genes per module. Cyclin-dependent kinase 1 ( CDK1), cyclin B1 ( CCNB1), and cell-division cycle protein 20 ( CDC20) hub genes were screened using the co-expression network. Furthermore, 17 GO terms and 6 KEGG pathways were identified, such as cell division, immune response process, and antigen processing and presentation. Two overlapping signaling pathways that are crucial factors in HBV-ALF were screened using the Comprehensive Toxicogenomics Database (CTD). Several candidate genes including HLA-E, B2M, HLA-DPA1, and SYK were associated with HBV-ALF progression. Natural killer cell-mediated cytotoxicity and antigen presentation contributed to the progression of HBV-ALF. The HLA-E, B2M, HLA-DPA1, and SYK genes play critical roles in the pathogenesis and development of HBV-ALF.

Publisher

SAGE Publications

Subject

Computer Science Applications,Genetics,Ecology, Evolution, Behavior and Systematics

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