Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach.
Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach.
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DOI：
10.1111/cas.12305
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发表时间：
2014-01
期刊：
影响因子：
5.7
通讯作者：
Nakayama J
中科院分区：
文献类型：
--
作者：
Shiratsu K;Higuchi K;Nakayama J
从胃粘膜下部分泌的胃腺粘蛋白含有独特的O-连接寡糖，其末端α 1，4-连接N-乙酰葡糖胺（αGlcNAc）残基主要连接至MUC 6支架。以前，我们产生了A4 gnt缺陷小鼠，完全缺乏αGlcNAc，并显示αGlcNAc作为胃癌的肿瘤抑制因子。为了确定αGlcNAc在胃癌中的临床病理学意义，我们检测了214例胃腺癌中αGlcNAc和粘蛋白表型标记物（包括MUC 5AC、MUC 6、MUC 2和CD 10）的免疫组化表达，并将这些表达模式与临床病理学参数和癌症特异性生存率进行了比较。在MUC 6阳性胃癌中评估αGlcNAc丢失。在54例分化型胃腺癌中，33例（61.1%）癌细胞中MUC 6缺乏αGlcNAc表达。αGlcNAc的缺失与分化型腺癌的浸润深度、分期和静脉浸润显著相关。αGlcNAc缺失也与MUC 6阳性分化型腺癌患者预后不良显著相关。相比之下，在未分化型腺癌中未观察到αGlcNAc丢失与任何临床病理变量之间的显著相关性。MUC 6的表达与分化型腺癌的临床病理变量也有显著相关性。然而，与αGlcNAc的情况不同，其表达与患者的癌症特异性生存期无关。在未分化型腺癌中，我们观察到粘蛋白表型标记物（包括MUC 6）表达与任何临床病理变量之间无显著相关性。这些结果共同表明，MUC 6阳性癌细胞中αGlcNAc的缺失与分化型胃腺癌的进展和不良预后相关，但与未分化型胃腺癌无关。
Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma.
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DOI：
10.1007/s00432-003-0499-6
发表时间：
2003-12-01
影响因子：
3.6
作者：
Mizoshita, T;Tsukamoto, T;Tatematsu, M
通讯作者：
Tatematsu, M
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
影响因子：
8.8
作者：
Peto R;Pike MC;Armitage P;Breslow NE;Cox DR;Howard SV;Mantel N;McPherson K;Peto J;Smith PG
通讯作者：
Smith PG
影响因子：
3.2
作者：
Nakajima, K;Ota, H;Nakayama, J
通讯作者：
Nakayama, J
影响因子：
29.4
作者：
DEBOLOS, C;GARRIDO, M;REAL, FX
通讯作者：
REAL, FX