Identification of aberrantly expressed glycans in gastric cancer by integrated lectin microarray and mass spectrometric analyses.
Identification of aberrantly expressed glycans in gastric cancer by integrated lectin microarray and mass spectrometric analyses.
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通过集成凝集素微阵列和质谱分析鉴定胃癌中异常表达的聚糖
DOI：
10.18632/oncotarget.13539
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Huang Z
中科院分区：
文献类型：
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作者：
Li X;Guan F;Li D;Tan Z;Yang G;Wu Y;Huang Z
癌症进展通常与聚糖表达模式的改变相关。胃癌是最常见的上皮癌类型，关于胃癌的总体糖组学知之甚少。我们整合凝集素芯片和质谱（MS）的方法来分析聚糖表达在三个胃癌细胞系（SGC-7901，HGC-27和MGC-803）和一个正常的胃上皮细胞系（GES-1）。通过凝集素染色和MALDI-TOF/TOF-MS证实了显著改变的聚糖。三种癌细胞系显示核心岩藻糖基化N-聚糖、GalNAcα-Ser/Thr（Tn抗原）和Sia 2 - 6 Gal β1-4GlcNAc N-聚糖水平升高，但双触角N-聚糖、Galβ1-3GalNAcα-Ser/Thr（T抗原）和（GlcNAc）n N-聚糖水平降低。采用凝集素组织化学方法检测胃癌组织中4种典型聚糖（核心岩藻糖基化、Sia 2 - 6 Gal β1-4GlcNAc、双触角N-聚糖、T抗原，分别由凝集素LCA、SNA、PHA-E+L和ACA识别）的异常表达。ACA结合能力较低与患者预后显著较差相关。我们的研究结果首次表明，由LCA，ACA和PHA-E+L识别的聚糖在胃癌中异常表达，并表明ACA是胃癌的潜在预后因素。
Cancer progression is usually associated with alterations of glycan expression patterns. Little is known regarding global glycomics in gastric cancer, the most common type of epithelial cancer. We integrated lectin microarray and mass spectrometry (MS) methods to profile glycan expression in three gastric cancer cell lines (SGC-7901, HGC-27, and MGC-803) and one normal gastric epithelial cell line (GES-1). Significantly altered glycans were confirmed by lectin staining and MALDI-TOF/TOF-MS. The three cancer cell lines showed increased levels of core-fucosylated N-glycans, GalNAcα-Ser/Thr (Tn antigen), and Sia2-6Galβ1-4GlcNAc N-glycans, but reduced levels of biantennary N-glycans, Galβ1-3GalNAcα-Ser/Thr (T antigen), and (GlcNAc)n N-glycans. Lectin histochemistry was used to validate aberrant expression of four representative glycans (core-fucosylation, Sia2-6Galβ1-4GlcNAc, biantennary N-glycans, T antigen, recognized respectively by lectins LCA, SNA, PHA-E+L, and ACA) in clinical gastric cancer samples. Lower binding capacity for ACA was correlated with significantly poorer patient prognosis. Our findings indicate for the first time that glycans recognized by LCA, ACA, and PHA-E+L are aberrantly expressed in gastric cancer, and suggest that ACA is a potential prognostic factor for gastric cancer.