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"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
Published on: February 19, 2019
Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated
Zhuo Li1,2, Na Zhang1, Zewen Dong2
1Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, P.R. China.
Insights
Abnormal fucosylation is crucial in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) progression. Multi-omic analysis reveals altered fucosyltransferases and fucosylated glycans, offering potential diagnostic biomarkers for HBV-HCC.
Area of Science:
- Oncology
- Glycoscience
- Hepatology
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally.
- Hepatitis B virus (HBV) is the primary risk factor for HCC in China.
- Aberrant glycoconjugates are linked to HBV-associated HCC (HBV-HCC) progression, but their role is not fully understood.
Purpose of the Study:
- To systematically investigate the dysregulation of glycoconjugates in HBV-HCC progression.
- To explore the potential of aberrant glycoconjugates as diagnostic and prognostic biomarkers for HBV-HCC.
Main Methods:
- Utilized an integrated strategy combining transcriptomics, glycomics, and glycoproteomics.
- Analyzed Gene Expression Omnibus (GEO) datasets for glyco-gene dysregulation.
- Performed glycomic and glycoproteomic analyses to assess N-glycans and glycoproteins.
Main Results:
- Discovered dysregulation of fucosyltransferases (FUTs) in liver tissues of HCC patients.
- Observed elevated levels of fucosylated N-glycans in HBV-HCC.
- Found progressive increases in fucosylation of IgA1 and IgG2.
Conclusions:
- Abnormal fucosylation plays a critical role in HBV-HCC progression.
- Integrative multi-omic analysis can identify aberrant glycoconjugates in tumor progression.
- These findings may lead to novel diagnostic and prognostic biomarkers for HBV-HCC.
Background:
Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker.
Methods:
An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC.
Results:
Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis.
Conclusions:
The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.
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