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鉴定 AAL 在萎缩性胃炎和胃癌患者唾液中识别的 N-和 O-连接聚糖。

Identification of N- and O-linked glycans recognized by AAL in saliva of patients with atrophic gastritis and gastric cancer.

机构信息

Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.

Department of Pothology, First People's Hospital of Chenzhou, Chenzhou, Hunan, China.

出版信息

Cancer Biomark. 2018;22(4):669-681. doi: 10.3233/CBM-171087.

Abstract

BACKGROUND AND AIM

Gastric cancer (GC) is a common and fatal malignancy with a worldwide occurrence. There still lacks effective biomarkers for precisely evaluating GC. Saliva is a biological fluid with enormous diagnostic potentials which emerged many advantages. We aimed to discover the novel biomarkers for accurately distinguishing early GC based on saliva glycopatterns.

METHODS

We used Aleuria Aurantia Lectin (AAL)-magnetic particle conjugates to isolate fucosylated glycoproteins in the pooled saliva of healthy volunteers (HV, n= 51) and patients with atrophic gastritis (AG, n= 51) or GC (n= 51), following to release the N- and O-linked glycans from the isolated proteins with PNGase F and NaClO, and further identified the released glycans by MALDI-TOF/TOF-MS, respectively.

RESULTS

A total of 9/9, 8/11, and 9/9 fucosylated N-/O-linked glycans were annotated in the isolated salivary proteins from HV, AG, and GC, respectively. Among these, six fucosylated N-linked glycansand four O-linked glycans exhibited significantly increased expression levels in GC, while five fucosylated N-linked glycans and ten fucosylated O-linked glycans exhibited significantly decreased expression levels in GC. The proportion of fucosylated N-linked glycans was decreased in GC (41.66%) compared with AG (43.63%) and HV (52.57%), as well as the fucosylated O-linked glycans was apparently decreased in GC (19.58%) compared with AG (25.43%) and HV (55.54%).

CONCLUSIONS

This study could provide pivotal information to distinguish among HV, AG, and GC, and facilitate the discovery of biomarkers for GC diagnosis based on precise alterations of N- and O-linked glycans in saliva.

摘要

背景与目的

胃癌(GC)是一种常见且致命的恶性肿瘤,在全球范围内都有发生。目前仍然缺乏能够准确评估 GC 的有效生物标志物。唾液是一种具有巨大诊断潜力的生物液体,具有许多优势。我们旨在发现基于唾液糖谱准确区分早期 GC 的新型生物标志物。

方法

我们使用 Aleuria Aurantia Lectin(AAL)-磁珠偶联物从健康志愿者(HV,n=51)、萎缩性胃炎(AG,n=51)和 GC 患者(n=51)的混合唾液中分离出岩藻糖基化糖蛋白,然后用 PNGase F 和 NaClO 从分离的蛋白质中释放 N-和 O-连接的聚糖,最后分别通过 MALDI-TOF/TOF-MS 鉴定释放的聚糖。

结果

从 HV、AG 和 GC 的唾液分离蛋白中分别注释了 9/9、8/11 和 9/9 个岩藻糖基化 N-/O-连接聚糖。其中,6 个岩藻糖基化 N-连接聚糖和 4 个 O-连接聚糖在 GC 中表达水平显著升高,而 5 个岩藻糖基化 N-连接聚糖和 10 个岩藻糖基化 O-连接聚糖在 GC 中表达水平显著降低。GC 中岩藻糖基化 N-连接聚糖的比例(41.66%)低于 AG(43.63%)和 HV(52.57%),GC 中岩藻糖基化 O-连接聚糖的比例(19.58%)明显低于 AG(25.43%)和 HV(55.54%)。

结论

本研究为区分 HV、AG 和 GC 提供了重要信息,并有助于发现基于唾液 N-和 O-连接聚糖精确改变的 GC 诊断标志物。

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