Reduced αGlcNAc glycosylation on gastric gland mucin is a biomarker of malignant potential for gastric cancer, Barrett's adenocarcinoma, and pancreatic cancer

Gastric gland mucin secreted from pyloric gland cells, mucous neck cells, and cardiac gland cells of the gastric mucosa harbors unique O-glycans carrying terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc), which are primarily attached to the scaffold mucin core protein MUC6. alpha GlcNAc acts as an antibiotic against Helicobacter pylori (H. pylori), a microbe causing gastric cancer. In addition, mice deficient in A4gnt, which encodes the enzyme alpha 1,4-N-acetylglucosaminyltransferase (alpha 4GnT) that catalyzes alpha GlcNAc biosynthesis, spontaneously develop gastric differentiated-type adenocarcinoma, even if not infected by H. pylori. Thus, alpha GlcNAc prevents gastric cancer as both an antibiotic and a tumor suppressor (Nakayama in Acta Histochem Cytochem 47:1-9, 2014b). Indeed, in humans alpha GlcNAc loss on MUC6 in differentiated-type adenocarcinoma is closely associated with poor patient prognosis (Shiratsu et al. in Cancer Sci 105:126-133, 2014). Recently, we reported reduced alpha GlcNAc expression on MUC6 in both pyloric gland adenoma of the stomach and chronic atrophic gastritis, in Barrett's esophagus, and in pancreatic intraductal papillary-mucinous neoplasm (IPMN)/pancreatic intraepithelial neoplasia (PanIN), all potentially premalignant conditions. This review discusses whether relatively reduced levels of alpha GlcNAc in these lesions could serve as a biomarker to predict malignant potential and cancer progression.