Decreased expression of TFF2 and decreased αGlcNAc glycosylation are malignant biomarkers of pyloric gland adenoma of the duodenum

被引:1
|
作者
Yamanoi, Kazuhiro [1 ,2 ]
Fujii, Chifumi [2 ,3 ,4 ]
Nakayama, Atsushi [5 ]
Matsuura, Noriko [5 ]
Takatori, Yusaku [5 ]
Kato, Motohiko [5 ]
Yahagi, Naohisa [5 ]
Nakayama, Jun [2 ]
机构
[1] Keio Univ, Sch Med, Dept Pathol, 35 Shinanomachi,Shinjuku, Tokyo 1608582, Japan
[2] Shinshu Univ, Dept Mol Pathol, Sch Med, Matsumoto, Japan
[3] Shinshu Univ, Inst Biomed Sci, Dept Biotechnol, Interdisciplinary Cluster Cutting Edge Res, Matsumoto, Japan
[4] Shinshu Univ, Ctr Med Educ & Clin Training, Sch Med, Matsumoto, Japan
[5] Keio Univ, Sch Med, Canc Ctr, Div Res & Dev Minimally Invas Treatment, Tokyo, Japan
基金
日本学术振兴会;
关键词
TREFOIL FACTORS; GASTRIC ADENOCARCINOMA; O-GLYCAN; MUCIN; PROGRESSION; ENTITY; LECTIN; FORMS;
D O I
10.1038/s41598-023-49040-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to alpha GlcNAc. We recently demonstrated that alpha GlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for alpha GlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. alpha GlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced alpha GlcNAc and TFF2 expression. The ratios of alpha GlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P < 0.001). Co-expression of alpha GlcNAc-glycosylated MUC6 and TFF2 in PGA suggests the existence of alpha GlcNAc/TFF2 form complex in PGA cells, a finding consistent with our observations in non-neoplastic Brunner's gland cells. The decreased alpha GlcNAc and TFF2 expression are associated with high grade atypical cells, indicative of the malignant potential of PGA.
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页数:10
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