Serum N‐acetylglucosaminyltransferase III activities in hepatocellular carcinoma

Abstract

N-Acetylglucosaminyltransferase III (GnT III) catalyses the addition of N-acetylglucosamine through a beta 1-4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin A (Con A)-reactive glycan into a non-reactive state. In this study, we measured GnT III activity to evaluate its diagnostic efficacy and its therapeutic effect on hepatocellular carcinoma (HCC). Concanavalin A-non-reactive fraction of serum transferrin (Tf) was also determined since the sugar chains of Tf are one of the possible candidates for the product of GnT III. Serum samples (159) were used from patients with HCC (89), liver cirrhosis (30), chronic hepatitis (19), alpha-fetoprotein (AFP) producing gastric carcinoma metastatic to the liver (five) and healthy controls (16). N-Acetylglucosaminyltransferase III activity was determined by high performance liquid chromatography. The reactivity of serum Tf to Con A was also analysed in 21 paired HCC samples before and after treatment by crossed immuno-affinoelectrophoresis. N-Acetylglucosaminyltransferase III activity from the HCC group (153 +/- 72pmol/mL/h) was significantly higher than that from liver cirrhosis (99 +/- 67 pmol/mL per h), chronic hepatitis (84 +/- 39 pmol/mL per h) and the normal controls (62 +/- 16 pmol/mL per h). N-Acetylglucosaminyltransferase III activity of 21 patients with HCC was significantly reduced after treatment such as transcatheter arterial chemoembolization and/or percutaneous ethanol infection therapy, (123 +/- 77 to 100 +/- 60 pmol/mL per h). Commensurate decreases of AFP and des-gamma-carboxy prothrombin with GnT III activity were also observed after treatment. The Con A-non-reactive fraction (n = 21; 6.4 +/- 2.3%) in patients with HCC after treatment was significantly lower than before (8.2 +/- 2.4%). The present study suggests that GnT III activity is a possible aid in the diagnosis and evaluation of HCC, especially when other tumour markers are negative.

The Hepatitis B Virus X Protein Inhibits Secretion of Apolipoprotein B by Enhancing the Expression of N-Acetylglucosaminyltransferase III

“…We also showed that GnT-III expression levels in HBx-transfected cells is higher than that in hepatocarcinoma HepG2 cells as well as GnT-IIItransfected cells, indicating that HBx induces GnT-III expression with strong GnT-III promotor activity. Therefore, this finding supports several studies which show that GnT-III expression may be involved in the development of HCC (23,25). Unfortunately, this study did not determine the precise promotor region involved in the activation for GnT-III expression by HBx because of the limitation of the comprehensive properties of the GnT-III promoter region (38,39), but this is the first report that HBx transactivates GnT-III expression.…”

Alteration of protein glycosylation in liver diseases

“…This enzyme was determined in hepatic nodules of humans and rats and the GnT-III activity in these nodules were shown to be significantly higher in contrast to its surrounding and the control liver [70][71][72]. These studies suggest a possible correlation between the GnT-III activity and the precancerous stage of hepatocarcinogenesis.…”

“…The activity of GnT-III in serum samples of HCC patients was determined by HPLC and it was significantly higher up-regulated in these patients in contrast to patients showing liver cirrhosis, chronic hepatitis and healthy controls. The GnT-III activity could be useful in HCC treatment follow-up because GnT-III activity is significantly reduced in HCC following percutaneous ethanol infection therapy and/or transcatheter arterial chemoembolization [71].…”

Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring

“…These alterations in the glycosylation of proteins were extensively studied in human tissues and especially in serum [13,15,25–27]. Other described alterations of glycans include increased branching, sialylation, agalactosylated glycans or polylactosamine chains [16,28,29]. …”