Glycosyltransferase B4GALNT2 as a Predictor of Good Prognosis in Colon Cancer: Lessons from Databases

Abstract

Background: glycosyltransferase B4GALNT2 and its cognate carbohydrate antigen Sda are highly expressed in normal colon but strongly downregulated in colorectal carcinoma (CRC). We previously showed that CRC patients expressing higher B4GALNT2 mRNA levels displayed longer survival. Forced B4GALNT2 expression reduced the malignancy and stemness of colon cancer cells. Methods: Kaplan–Meier survival curves were determined in “The Cancer Genome Atlas” (TCGA) COAD cohort for several glycosyltransferases, oncogenes, and tumor suppressor genes. Whole expression data of coding genes as well as miRNA and methylation data for B4GALNT2 were downloaded from TCGA. Results: the prognostic potential of B4GALNT2 was the best among the glycosyltransferases tested and better than that of many oncogenes and tumor suppressor genes; high B4GALNT2 expression was associated with a lower malignancy gene expression profile; differential methylation of an intronic B4GALNT2 gene position and miR-204-5p expression play major roles in B4GALNT2 regulation. Conclusions: high B4GALNT2 expression is a strong predictor of good prognosis in CRC as a part of a wider molecular signature that includes ZG16, ITLN1, BEST2, and GUCA2B. Differential DNA methylation and miRNA expression contribute to regulating B4GALNT2 expression during colorectal carcinogenesis.

Comparative Gene Signature of (−)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights

“…Low HHEX expression is common in TNBC and hormone-negative and basal-like BCs [ 70 ]. Furthermore, β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) is a biosynthetic enzyme of histo-blood group antigens Sda antigen, a natural component of the red blood cells in the healthy colon of a vast majority of people [ 71 ]. Prior studies have shown that the downregulation of B4GALNT2 can be a marker for colon and gastrointestinal cancers [ 71 , 72 ].…”

“…Furthermore, β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) is a biosynthetic enzyme of histo-blood group antigens Sda antigen, a natural component of the red blood cells in the healthy colon of a vast majority of people [ 71 ]. Prior studies have shown that the downregulation of B4GALNT2 can be a marker for colon and gastrointestinal cancers [ 71 , 72 ]. Direct upregulation of the B4GALNT2 gene level reduces the colon malignancy and the stem-associated malignant phenotype in a highly selective fashion [ 73 ].…”

Recent Advances in Exosome-Based Drug Delivery for Cancer Therapy

“…Besides adding targeting ligands to the exosome surface, it is also possible to alter the targeting ability of exosomes by removing endogenous surface molecules. Glycosyltransferases, which control the composition of glycome, are strongly associated with cancer progression [148,149]. Glycosylation of lipids and proteins on cellular surfaces plays an important role in cancer metastasis and glycan sialic acid, which is deeply involved in cancer metastasis, was found on the surface of exosomes [150,151].…”

The Cancer-Associated Antigens Sialyl Lewisa/x and Sda: Two Opposite Faces of Terminal Glycosylation

“…Interestingly, the glycosylation machinery is also differentially expressed in HBE and LBE. In fact, several glycosyltransferases involved in the biosynthesis of O-linked chains, gangliosides, Lewis antigens, and galectins are more highly expressed in HBE, while ST6GAL sialyltransferases are more highly expressed in LBE [ 42 ].…”

“…The mechanisms regulating B4GALNT2 expression in normal and cancer tissues are probably multifactorial and partially epigenetic. TCGA data allow a detailed analysis of the relationship between B4GALNT2 expression and methylation of individual methylation sites located in the CpG island, as well as in its upstream and downstream flanking regions known as “northern shore (NS)” and “southern shore (SS)”, respectively [ 42 ] ( Figure 4 ). In addition, the methylation of an “open sea (OS)” site located in the intron between exons 6 and 7 was also reported.…”