Dataset Information

The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.

ABSTRACT:

Objectives

Mutations in hepatitis B virus (HBV) X region (HBx) play important roles in hepatocarcinogenesis while the results remain controversial. We sought to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in HBx from HBV genotype C-infected patients and the distribution of those mutations in different disease phases and genotypes.

Methods

HBx sequences downloaded from an online global HBV database were screened and then classified into Non-HCC or HCC group by diagnosis information. Patients' data of patient age, gender, country or area, and viral genotype were also extracted. Logistic regression was performed to evaluate the effects of mutations on HCC risk.

Results

1) Full length HBx sequences (HCC: 161; Non-HCC: 954) originated from 1115 human sera across 29 countries/areas were extracted from the downloaded 5956 HBx sequences. Genotype C occupied 40.6% of Non-HCC (387/954) and 89.4% of HCC (144/161). 2) Sixteen nucleotide positions showed significantly different distributions between genotype C HCC and Non-HCC groups. 3) Logistic regression showed that mutations A1383C (OR: 2.32, 95% CI: 1.34-4.01), R1479C/T (OR: 1.96, 95% CI: 1.05-3.64; OR: 5.15, 95% CI: 2.53-10.48), C1485T (OR: 2.40, 95% CI: 1.41-4.08), C1631T (OR: 4.09, 95% CI: 1.41-11.85), C1653T (OR: 2.58, 95% CI: 1.59-4.19), G1719T (OR: 2.11, 95% CI: 1.19-3.73), and T1800C (OR: 23.59, 95% CI: 2.25-247.65) were independent risk factors for genotype C HBV-related HCC, presenting different trends among individual disease phases. 4) Several genotype C HCC risk mutations pre-existed, even as major types, in early disease phases with other genotypes.

Conclusions

Mutations associated with HCC risk were mainly located in HBx transactivation domain, viral promoter, protein/miRNA binding sites, and the area for immune epitopes. Furthermore, the signatures of these mutations were unique to disease phases leading to HCC, suggesting molecular counteractions between the virus and host during hepatocarcinogenesis.

SUBMITTER: Li W

PROVIDER: S-EPMC4420286 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.

Li Wenwen W Goto Kaku K Matsubara Yasuo Y Ito Sayaka S Muroyama Ryosuke R Li Qiang Q Kato Naoya N

PloS one 20150505 5

<h4>Objectives</h4>Mutations in hepatitis B virus (HBV) X region (HBx) play important roles in hepatocarcinogenesis while the results remain controversial. We sought to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in HBx from HBV genotype C-infected patients and the distribution of those mutations in different disease phases and genotypes.<h4>Methods</h4>HBx sequences downloaded from an online global HBV database were screened and then classified into Non-HCC or HCC ...[more]

PMID: 25942596

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Project description:Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, CDCA5, CENPH, and MCM7, and 4 novel genes, namely, CDC6, CDC45, CDCA8, and MCM4, which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The CDCA8 and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis.

Dataset Information

The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.

Objectives

Methods

Results

Conclusions

Publications

The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.

Similar Datasets

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