Association between the alteration of serum N-glycan profile and the change of glycosyltransferase expression in liver tissue in patients with hepatitis B virus-related hepatocellular carcinoma / 临床肝胆病杂志

ABSTRACT

ObjectiveTo investigate the potential mechanism of serum N-glycan alterations in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by measuring serum N-glycan profile and comparing glycosyltransferase gene expression between HCC tissue and adjacent tissue. MethodsThe samples of HCC tissue, adjacent tissue, and normal liver tissue were collected from 34 patients with HBV-related HCC who were admitted to Chinese PLA General Hospital, and serum samples were also collected. Among these 34 patients, 8 were randomly selected and their serum samples were established as HCC experimental group, and the serum samples of 20 healthy adults were established as control group. DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis was used to analyze serum N-glycan profile in the HCC experimental group and the control group. Quantitative real-time PCR was used to measure the mRNA expression of 8 glycosyltransferase genes (FUT3, FUT4, FUT6, FUT7, FUT8, Gn-TIII, Gn-TIVa, and Gn-TV) in the HCC tissue and adjacent tissue of 34 patients with HBV-related HCC, and Western blot was used to measure the expression of corresponding proteins. The independent samples t-test was used for comparison of continuous data between two groups. ResultsCompared with the control group, the HCC experimental group had a significant increase in the abundance of N-glycan peak9 (NA3Fb) in serum(t=-2.514,P＜0.05). There were significant differences in the mRNA expression of FUT8, Gn-TIVa, and Gn-TV between HCC tissue and adjacent tissue, and the mRNA and protein expression levels of FUT8 and Gn-TV in HCC tissue were significantly higher than those in adjacent tissue (FUT8 mRNA 1.50±0.34 vs 0.65±0.11, t=-2.354，P=0.022; Gn-TV mRNA 3.57±0.64 vs 1.33±016, t=-3.384,P=0001; FUT8 protein 0.70±0.11 vs 0.083±0.017, t=9.555,P=0.001; Gn-TV protein 1.33±0.19 vs 0.60±0.15, t=5.097,P=0.007). The mRNA expression level of Gn-TIVa in HCC tissue was significantly higher than that in adjacent tissue (2.90±0.47 vs 1.68±0.19, t=-2.403,P=0.019), but there was no significant difference in the protein expression level of Gn-TIVa between HCC tissue and adjacent tissue (052±0.24 vs 0.24±0.11,t=1.833, P=0.141). The changes of glycosyltransferase gene expression in HCC tissue were consistent with the alteration of serum N-glycan profile. ConclusionSerum N-glycan alterations in patients with HBV-related HCC may be closely associated with the upregulated expression of the glycosyltransferase genes FUT8, Gn-TIVa, and Gn-TV in HCC tissue.