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利用凝集素芯片技术对早期胃癌进行糖谱分析。

Glycoprofiling of Early Gastric Cancer Using Lectin Microarray Technology.

作者信息

Li Taijie, Mo Cuiju, Qin Xue, Li Shan, Liu Yinkun, Liu Zhiming

出版信息

Clin Lab. 2018 Jan 1;64(1):153-161. doi: 10.7754/Clin.Lab.2017.170814.

Abstract

BACKGROUND

Recently, studies have reported that protein glycosylation plays an important role in the occurrence and development of cancer. Gastric cancer is a common cancer with high morbidity and mortality owing to most gastric cancers are discovered only at an advanced stage. Here, we aim to discover novel specific serum glycanbased biomarkers for gastric cancer.

METHODS

A lectin microarray with 50 kinds of tumor-associated lectin was used to detect the glycan profiles of serum samples between early gastric cancer and healthy controls. Then lectin blot was performed to validate the differences.

RESULTS

The result of the lectin microarray showed that the signal intensities of 13 lectins showed significant differences between the healthy controls and early gastric cancer. Compared to the healthy, the normalized fluorescent intensities of the lectins PWA, LEL, and STL were significantly increased, and it implied that their specifically recognized GlcNAc showed an especially elevated expression in early gastric cancer. Moreover, the binding affinity of the lectins EEL, RCA-II, RCA-I, VAL, DSA, PHA-L, UEA, and CAL were higher in the early gastric cancer than in healthy controls. These glycan structures containing GalNAc, terminal Galβ 1-4 GlcNAc, Tri/tetraantennary N-glycan, β-1, 6GlcNAc branching structure, α-linked fucose residues, and Tn antigen were elevated in gastric cancer. While the two lectins CFL GNL reduced their binding ability. In addition, their specifically recognized N-acetyl-D-galactosamine structure and (α-1,3) mannose residues were decreased in early gastric cancer. Furthermore, lectin blot results of LEL, STL, PHA-L, RCA-I were consistent with the results of the lectin microarray.

CONCLUSIONS

The findings of our study clarify the specific alterations for glycosylation during the pathogenesis of gastric cancer. The specific high expression of GlcNAc structure may act as a potential early diagnostic marker for gastric cancer.

摘要

背景

最近,有研究报道蛋白质糖基化在癌症的发生和发展中起重要作用。胃癌是一种常见癌症,由于大多数胃癌在晚期才被发现,其发病率和死亡率都很高。在此,我们旨在发现用于胃癌的新型特异性血清聚糖生物标志物。

方法

使用含有50种肿瘤相关凝集素的凝集素微阵列检测早期胃癌患者和健康对照者血清样本的聚糖谱。然后进行凝集素印迹法以验证差异。

结果

凝集素微阵列结果显示,13种凝集素的信号强度在健康对照者和早期胃癌患者之间存在显著差异。与健康对照相比,凝集素PWA、LEL和STL的标准化荧光强度显著增加,这表明它们特异性识别的GlcNAc在早期胃癌中表达特别升高。此外,凝集素EEL、RCA-II、RCA-I、VAL、DSA、PHA-L、UEA和CAL在早期胃癌中的结合亲和力高于健康对照者。这些含有GalNAc、末端Galβ1-4GlcNAc、三/四天线N-聚糖、β-1,6GlcNAc分支结构、α-连接的岩藻糖残基和Tn抗原的聚糖结构在胃癌中升高。而两种凝集素CFL、GNL的结合能力降低。此外,它们特异性识别的N-乙酰-D-半乳糖胺结构和(α-1,3)甘露糖残基在早期胃癌中减少。此外,LEL、STL、PHA-L、RCA-I的凝集素印迹结果与凝集素微阵列结果一致。

结论

我们的研究结果阐明了胃癌发病机制中糖基化的具体改变。GlcNAc结构的特异性高表达可能作为胃癌潜在的早期诊断标志物。

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