Decreased expression of gastric gland mucin‐specific glycan α1,4‐linked <i>N</i>‐acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach

Yamanoi, Kazuhiro; Sekine, Shigeki; Higuchi, Kayoko; Kushima, Ryoji; Nakayama, Jun

doi:10.1111/his.12728

Cited by 13 publications

(21 citation statements)

References 18 publications

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“…In support of this idea, we observed that αGlcNAc expression is frequently lost in human gastric differentiated‐type adenocarcinoma expressing MUC6 . We also showed that reduced αGlcNAc expression relative to MUC6 is associated with malignant potential in pyloric gland adenoma of the human stomach, a precursor of gastric adenocarcinoma . These studies suggest overall that αGlcNAc could serve as a critical biomarker of malignant potential in early stages of gastric epithelial neoplasias.…”

supporting

confidence: 72%

“…In the present study, we reveal that at the early phase of PanIN‐IDAC and of IPMN‐IPMNAIC sequence, MUC6 expression significantly predominates over αGlcNAc expression, and as histological grade progresses to pancreatic cancer, expression levels of both decrease. We recently demonstrated that αGlcNAc expression is significantly reduced in pyloric gland adenoma with high‐grade dysplasia that is a precancerous lesion of gastric adenocarcinoma . These results overall suggest that reduced αGlcNAc expression relative to MUC6 occurs at early stages of pancreatic tumor progression.…”

Section: Discussionmentioning

confidence: 84%

“…First, lesions in which >5% of the total number of tumor cells of each lesion were positively‐stained were judged positive, as described previously . Second, expression levels of MUC6 and αGlcNAc were further scored semi‐quantitatively from 0 to 3: 0 (≤5% positive cells), 1 (6%–33% positive cells), 2 (34%–66% positive cells) or 3 (≥67% positive cells), as described previously …”

Section: Methodsmentioning

confidence: 99%

“…(15) Second, expression levels of MUC6 and aGlcNAc were further scored semi-quantitatively from 0 to 3: 0 (≤5% positive cells), 1 (6%-33% positive cells), 2 (34%-66% positive cells) or 3 (≥67% positive cells), as described previously. (16) Statistical analysis. Correlations between each grade for PanIN or IPMN and the number of positive lesions were statistically analyzed by Fisher's exact probability test.…”

Section: Methodsmentioning

confidence: 99%

“…(15) We also showed that reduced aGlcNAc expression relative to MUC6 is associated with malignant potential in pyloric gland adenoma of the human stomach, a precursor of gastric adenocarcinoma. (16) These studies suggest overall that aGlcNAc could serve as a critical biomarker of malignant potential in early stages of gastric epithelial neoplasias. In normal human pancreas, MUC6 and aGlcNAc are coexpressed in periductal mucous gland cells of the main pancreatic duct.…”

mentioning

confidence: 93%

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Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

et al. 2017

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Pancreatic cancer is lethal, as it is often detected late. Thus, novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin‐specific O‐glycans are unique in having α1,4‐linked N‐acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated‐type gastric adenocarcinoma (Karasawa et al., J Clin Invest 122, 923, 2012). MUC6 is also expressed in pancreatic neoplasms, including PanIN and IPMN, but the role of αGlcNAc expression in pancreatic neoplasms remains unknown. Here, we analyze expression patterns of αGlcNAc, MUC6 and MUC5AC in pancreatic neoplasms and compare them with progression from PanIN to invasive ductal adenocarcinoma (IDAC) (the PanIN‐IDAC sequence; 20 cases) and from IPMN to IPMN with associated invasive carcinoma (IPMNAIC) (the IPMN‐IPMNAIC sequence; 20 cases). At both sequences, the frequency of MUC6‐positive and αGlcNAc‐positive lesions decreased with tumor progression. We then compared expression levels of αGlcNAc and MUC6 at each step of the progression. At the PanIN‐IDAC sequence, αGlcNAc expression significantly decreased relative to MUC6 in low‐grade PanIN (P = 0.021), high‐grade PanIN/intraductal spread of IDAC (P = 0.031) and IDAC (P = 0.013). At the IPMN‐IPMNAIC sequence, decreased αGlcNAc expression was also observed in low‐grade IPMN exhibiting gastric‐type morphology (P = 0.020). These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early and marks the initiation of tumor progression to pancreatic cancer.

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supporting

confidence: 72%

Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 93%

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Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

et al. 2017

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

Yamanoi

Nakayama

2018

Histochem Cell Biol

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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 α1,4-linked N-acetylglucosamine residues (αGlcNAc), which are primarily attached to the scaffold mucin core protein MUC6. αGlcNAc acts as an antibiotic against Helicobacter pylori (H. pylori), a microbe causing gastric cancer. In addition, mice deficient in A4gnt, which encodes the enzyme α1,4-N-acetylglucosaminyltransferase (α4GnT) that catalyzes αGlcNAc biosynthesis, spontaneously develop gastric differentiated-type adenocarcinoma, even if not infected by H. pylori. Thus, αGlcNAc prevents gastric cancer as both an antibiotic and a tumor suppressor (Nakayama in Acta Histochem Cytochem 47:1-9, 2014b). Indeed, in humans αGlcNAc 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 αGlcNAc 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 αGlcNAc in these lesions could serve as a biomarker to predict malignant potential and cancer progression.

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MUC6 expression is a preferable prognostic marker for invasive mucinous adenocarcinoma of the lung

Yamanoi

Fujii

Yuzuriha

et al. 2022

Histochem Cell Biol

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Decreased expression of gastric gland mucin‐specific glycan α1,4‐linked N‐acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach

Cited by 13 publications

References 18 publications

Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

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

MUC6 expression is a preferable prognostic marker for invasive mucinous adenocarcinoma of the lung

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