Clinicopathological significance of core 3 O-glycan synthetic enzyme, β1,3-N-acetylglucosaminyltransferase 6 in pancreatic ductal adenocarcinoma.
Clinicopathological significance of core 3 O-glycan synthetic enzyme, β1,3-N-acetylglucosaminyltransferase 6 in pancreatic ductal adenocarcinoma.
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DOI：
10.1371/journal.pone.0242851
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Hiraoka N
中科院分区：
文献类型：
--
作者：
Doi N;Ino Y;Angata K;Shimada K;Narimatsu H;Hiraoka N
粘蛋白型O-聚糖参与癌症的发生和发展，尽管其生物学和临床病理学作用的细节仍不清楚。本研究旨在探讨β 1，3-N-乙酰葡糖胺转移酶6（β 3Gn-T6）在胰腺导管腺癌（PDAC）中的临床病理意义。应用免疫组化和凝集素组织化学方法检测156例PDAC合并胰腺上皮内瘤变（PanINs）及相应正常胰腺组织中β 3Gn-T6和几种O-聚糖的表达。PDAC细胞中T抗原、Tn抗原、唾液酸刘易斯X（sLeX）抗原和核心2 O-聚糖上的sLeX的表达高于正常胰腺导管上皮细胞（NPDE）。相反，在NPDE中发现了延伸的核心10-聚糖上的6-磺基N-乙酰乳糖胺的表达，并且在PDAC细胞中低。这些聚糖表达水平与患者结局无关。β 3Gn-T6在约20%的PDAC病例和30 - 40%的PanIN中表达，但在NPDE中不表达。在单因素和多因素分析中，在分化程度更高的腺癌病例中发现PDAC细胞中β 3Gn-T6表达更高，显示无病生存期显著更长。此外，β 3Gn-T6在PDAC细胞和PanINs中的表达与MUC5AC在这些细胞中的表达显著相关，提示β 3Gn-T6表达与胃小凹表型的细胞分化状态有关。因此，PDAC细胞中的β 3 Gn-T6表达可能是PDAC患者的有利预后因素，并且β 3 Gn-T6的表达与胰腺癌发生中的胃小凹表型相关。
Mucin-type O-glycans are involved in cancer initiation and progression, although details of their biological and clinicopathological roles remain unclear. The aim of this study was to investigate the clinicopathological significance of β1,3-N-acetylglucosaminyltransferase 6 (β3Gn-T6), an essential enzyme for the synthesis of core 3 O-glycan and several other O-glycans in pancreatic ductal adenocarcinoma (PDAC). We performed immunohistochemical and lectin-histochemical analyses to detect the expression of β3Gn-T6 and several O-glycans in 156 cases of PDAC with pancreatic intraepithelial neoplasias (PanINs) and corresponding normal tissue samples. The T antigen, Tn antigen, sialyl Lewis X (sLeX) antigen, and sLeX on core 2 O-glycan were more highly expressed in PDAC cells than in normal pancreatic duct epithelial cells (NPDEs). Conversely, the expression of 6-sulfo N-acetyllactosamine on extended core 1 O-glycan was found in NPDEs and was low in PDAC cells. These glycan expression levels were not associated with patient outcomes. β3Gn-T6 was expressed in ~20% of PDAC cases and 30–40% of PanINs but not in NPDEs. Higher expression of β3Gn-T6 was found in PDAC cells in more differentiated adenocarcinoma cases showing significantly longer disease-free survival in both univariate and multivariate analyses. In addition, the expression of β3Gn-T6 in PDAC cells and PanINs significantly correlated with the expression of MUC5AC in these cells, suggesting that β3Gn-T6 expression is related to cellular differentiation status of the gastric foveolar phenotype. Thus, it is likely that β3Gn-T6 expression in PDAC cells is a favorable prognostic factor in PDAC patients, and that the expression of β3Gn-T6 correlates with the gastric foveolar phenotype in pancreatic carcinogenesis.
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影响因子：
4.6
作者：
Magalhães A;Rossez Y;Robbe-Masselot C;Maes E;Gomes J;Shevtsova A;Bugaytsova J;Borén T;Reis CA
通讯作者：
Reis CA
DOI：
10.1083/jcb.107.5.1853
发表时间：
1988-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Streeter PR;Rouse BT;Butcher EC
通讯作者：
Butcher EC
影响因子：
4.1
作者：
Robbe, C;Capon, C;Michalski, JC
通讯作者：
Michalski, JC
DOI：
10.1006/bbrc.1998.8824
发表时间：
1998-06-18
影响因子：
3.1
作者：
Kumamoto, K;Mitsuoka, C;Kannagi, R
通讯作者：
Kannagi, R
影响因子：
3
作者：
Mitoma, Junya;Miyazaki, Tatsuo;Sutton-Smith, Mark;Suzuki, Misa;Saito, Hideo;Yeh, Jiunn-Chern;Kawano, Takehiro;Hindsgaul, Ole;Seeberger, Peter H.;Panico, Maria;Haslam, Stuart M.;Morris, Howard R.;Cummings, Richard D.;Dell, Anne;Fukuda, Minoru
通讯作者：
Fukuda, Minoru