The glycosyltransferases B4GALNT3 and B4GALT3 were mistakenly analyzed as B4GALNT3 in this review. The Table 1 was changed and the text in the last paragraph of “Glycosyltransferases as tumor markers in NB patients” was modified as follows.
Table 1.
Glycosyltransferases as neuroblastoma (NB) tumor markers.
| Enzyme | Method/sample | Clinical significance | Reference |
|---|---|---|---|
| β1,4-N-acetylgalactosaminyltransferase (GD2 synthase) | ICC/bone marrow | Molecular marker of metastatic NB | J Clin Oncol; 4:363–369 (1986) |
| RT-PCR ECL/bone marrow | Molecular marker of metastatic NB | Cancer; 92:924–931 (2001) | |
| RT-PCR ECL/bone marrow | Molecular marker of metastatic NB | Am J Pathol; 159:493–500 (2001) | |
| qRT-PCR/bone marrow | Marker for minimal residual disease | J Clin Oncol; 21:1087–1093 (2003) | |
| qRT-PCR/bone marrow-PB | Prognostic marker (poor outcome) | Int J Cancer; 123:2849–2855 (2008) | |
| Sialyltransferase STX (ST8SiaII) | qRT-PCR/bone marrow | Molecular marker of metastatic NB | Int. Cancer; 119:152–156 (2006) |
| N-acetylglucosaminyltransferase V (GnT-V) | qRT-PCR/primary tumor | Prognostic marker (better outcome) | FEBS Lett; 580:627–632 (2006) |
| UDP-polypeptide GalNAc-transferase 13 (GalNAc-T13 – GALNT13) | RT-PCR/bone marrow | Molecular marker of metastatic NB | Clin Chem; 52:1701–1712 (2006) |
| UDP-polypeptide GalNAc-transferase 9 (GalNAc-T9 – GALNT9) | RT-PCR/primary tumor | Prognostic marker (better outcome) | Clin Chem; 59(1):225–233 (2013) |
| β1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) | IHC/primary tumor | Prognostic marker (better outcome) | Cancer Sci; 104:1600–1608 (2013) |
| β1,4-N-acetylgalactosaminyltransferase 3 (B4GALNT3) | IHC/primary tumor | Prognostic marker (better outcome) | Am J Pathol; 179:1394–1404 (2011) |
| β-1,4-galactosyltransferase III (B4GALT3) | IHC/primary tumor | Prognostic marker (poor outcome) | Clin Cancer Res; 19:1705–1716 (2013) |
ICC, immunocytochemistry; RT-PCR, reverse transcriptase-polymerase chain reaction; ECL, electrochemiluminescence; PB, peripheral blood; IHC, immunohistochemistry.
β1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) cloned by Sato et al., has been described as expressed in stomach, colon, and testis (136). This enzyme can transfer GalNAc residues to non-reducing terminal GlcNAc-β leading to the synthesis of GalNAcβ1–4GlcNAc (also known as LacdiNAc or LDN), which is a unique terminal structure in the outer chain moieties of human N-glycans (137), and also in O-linked oligosaccharide structures (138). The largest amount of B4GALNT3 transcripts were found in gastric tissues, followed by colon, testis, and adrenal glands (136). Gastric expression of B4GALNT3 was found regulated by cellular differentiation (139). In the human colon, Huang et al. reported that B4GALNT3 is up-regulated in primary tumors comparing with the normal mucosa (140). They performed in vitro and in vivo experiments showing that overexpression of this enzyme increases malignant phenotype of colon cancer cells, and these phenotypic changes are associated with enhanced integrin and mitogen-activated protein kinase (MAPK) signaling, suggesting that B4GALNT3 may play a crucial role in promoting malignant behavior of colon cancer (140). The same research team has recently published that β-1,4-galactosyltransferase III (B4GALT3) overexpression in colorectal cancer cells suppressed cell migration, invasion, and adhesion, while B4GALT3 knockdown enhanced malignant cell phenotypes promoting cell migration and invasion (141). Surprisingly, an opposite situation was found for both enzymes in NB. Firstly Hsu et al. communicated that B4GALNT3 expression positively correlates with the differentiation status of NB, predicting a favorable prognosis for patients and suppressing the malignant phenotype in cell lines experiments via decreasing β1-integrin signaling (142). By contrast, β-1,4-galactosyltransferase III (B4GALT3) expression in NB tumors correlated with advanced clinical stage, unfavorable histology, and lower survival rate (143). In conclusion, B4GALNT3 in NB seems a good prognostic marker, while B4GALT3 was suggested as poor outcome marker. Further work is necessary to elucidate subjacent molecular mechanisms for these enzymes.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.