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Published on: May 4, 2012
Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B-
Xinmin Qin1, Yonghong Guo2, Haoqi Du1
1Laboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityXi'an, China.
Insights
This study reveals distinct serum glycoprotein glycopatterns in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients. These glycopattern differences may serve as novel biomarkers for distinguishing between CHB and CHC infections.
Area of Science:
- Biochemistry
- Hepatology
- Glycomics
Background:
- Chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are leading causes of cirrhosis and hepatocellular carcinoma.
- Distinct pathogenic processes underlie CHB and CHC infections.
- Serum glycoprotein glycopattern differences between CHB and CHC patients remain largely uncharacterized.
Purpose of the Study:
- To investigate and compare serum glycoprotein glycopatterns between CHB and CHC patients.
- To identify potential glycan-based biomarkers for differentiating CHB from CHC.
Main Methods:
- Utilized lectin microarrays and lectin-mediated affinity capture for serum glycoprotein analysis.
- Employed MALDI-TOF/TOF-MS to identify specific glycan structures.
- Validated findings using lectin blotting and compared glycopatterns across CHB, CHC, and healthy volunteer groups.
Main Results:
- Identified unique lectin expression patterns for CHB (e.g., increased HHL, GSL-II, EEL; decreased LCA, VVA, ACA) and CHC (e.g., decreased DBA; increased WGA, SNA).
- Observed a common increasing trend for LEL and MAL-I in both CHB and CHC patients compared to healthy volunteers.
- Discovered specific N-glycan profiles, including 3 peaks unique to CHC patients and 5 peaks in virus-infected hepatitis patients compared to healthy volunteers.
Conclusions:
- Serum glycoprotein glycopatterns exhibit significant, distinct alterations in CHB and CHC.
- Specific glycan structures and lectin expression levels can differentiate between CHB and CHC.
- These findings offer valuable insights for developing novel glycopattern-based biomarkers for CHB/CHC diagnosis.
Abstract:
Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients. Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35). Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns. Finally, the differences of the glycoprotein glycopatterns were systematically compared between CHB and CHC patients. Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients. However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients. Furthermore, LEL and MAL-I showed a coincidentally increasing trend in both CHC and CHB patients compared with the HV. The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients. Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01). The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients. Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
