The B-Cell-Specific Ablation of B4GALT1 Reduces Cancer Formation and Reverses the Changes in Serum IgG Glycans during the Induction of Mouse Hepatocellular Carcinoma

SIMPLE SUMMARY: As serum IgG glycosylation is associated with various cancers, our goal is to explore whether serum IgG galactosylation and its associated glycans could be used as tumor markers associated with hepatocellular carcinoma (HCC). At the same time, we explore the effect of the B-cell-specific ablation of B4GALT1 on HCC and finally analyze whether the low incidence of female cancer was related to the findings from the above perspective. The results demonstrate that the tumor marker of serum IgG glycosylation is galactosylation and its associated glycans and that the B-cell-specific ablation of B4GALT1 reduces HCC formation by reducing serum IgG galactosylation levels and by modulating the associated glycans, meaning that the lower incidence of cancer in women may be related to minor changes in the B-cell B4GALT1 and unchanged serum IgG galactosylation levels. This study aims to provide a theoretical basis for the early diagnosis and prevention of HCC and to determine why it has such a high incidence in males. ABSTRACT: Serum immunoglobulin G (IgG) glycosylation, especially galactosylation, has been found to be related to a variety of tumors, including hepatocellular carcinoma (HCC). However, whether IgG glycan changes occur in the early stages of HCC formation remains unclear. We found that the galactosylation level increased and that the related individual glycans showed regular changes over the course of HCC induction. Then, the effect of the B-cell-specific ablation of β1,4galactosyltransferase 1 (CKO B4GALT1) and B4GALT1 defects on the IgG glycans that were modified during the model induction process and HCC formation is investigated in this study. CKO B4GALT1 reduces serum IgG galactosylation levels and reduces cancer formation. Furthermore, insignificant changes in the B-cell B4GALT1 and unchanged serum IgG galactosylation levels were found during cancer induction in female mice, which might contribute to the lower cancer incidence in female mice than in male mice. The gender differences observed during glycan and B4GALT1 modification also add more evidence that the B4GALT1 in B cells and in serum IgG galactosylation may play an important role in HCC. Therefore, the findings of the present research can be used to determine the methods for the early detection of HCC as well as for prevention.