Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder
Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder
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DOI：
10.1007/s00535-013-0813-2
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发表时间：
2014-04-01
影响因子：
6.3
通讯作者：
Shoda, Junichi
中科院分区：
文献类型：
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作者：
Onuki, Kenichiro;Sugiyama, Hiroaki;Shoda, Junichi
N-乙酰葡糖胺转移酶V（GnT-V）是一种催化N-乙酰葡糖胺在细胞蛋白的天冬酰胺连接寡糖上的β 1-6分支的酶，可增强实验模型中癌细胞的恶性行为。为探讨GnT-V在pT（2）型胆囊癌中表达的临床意义，采用体外实验方法，对90例pT（2）型胆囊癌进行了GnT-V表达的检测。用小干扰RNA（siRNA）诱导不同GnT-V表达水平的胆囊癌细胞，观察GnT-V的体内外生物学效应，结果90例胆囊癌中57例呈阳性表达，33例呈阴性表达，其中31例为颗粒型，26例为弥漫型。在76例根治性切除的病例中，阳性染色者的术后生存率明显低于阴性染色者（P = 0.028）。在所有的76例中，术后复发在那些显示弥漫型定位显着更频繁比那些显示阴性染色。实验分析表明，GnT-V在胆囊癌细胞中的表达下调诱导细胞生长抑制体外。GnT-V在胆囊癌细胞中的表达水平与胆囊癌细胞在体内的快速生长、血管生成增强、易形成肝转移密切相关，GnT-V在pT（2）胆囊癌浆膜下层的表达与胆囊癌的侵袭性密切相关。
N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the beta 1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT(2) gallbladder carcinoma with simple in vitro experiments.Ninety patients with pT(2) gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA.Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis.GnT-V expression in the subserosal layer of pT(2) gallbladder carcinoma is correlated with the aggressiveness of the disease.