Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics.
Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics.
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基于定量糖组学发现上皮性卵巢癌中与转移相关的特定 N-聚糖改变
DOI：
10.1371/journal.pone.0087978
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Zhang X;Wang Y;Qian Y;Wu X;Zhang Z;Liu X;Zhao R;Zhou L;Ruan Y;Xu J;Liu H;Ren S;Xu C;Gu J
一般情况下，大多数卵巢癌只有在发生大范围和远处转移时才能被发现，这是卵巢癌高死亡率的主要原因。因此，寻找卵巢癌转移相关的生物标志物以检测卵巢癌的隐匿性转移已成为当务之急。糖基化改变是恶性肿瘤的普遍特征，某些类型的聚糖结构是肿瘤进展的众所周知的标志物。因此，本研究旨在揭示转移性卵巢癌分泌组中N-聚糖的特异性变化。我们采用基于代谢稳定同位素标记的定量糖组学方法，比较卵巢癌细胞系SKOV 3及其高转移衍生物SKOV 3-ip之间分泌组的差异N-糖基化。有趣的是，在鉴定的总共17种N-聚糖中，与SKOV 3相比，SKOV 3-ip中具有二等分GlcNAc的N-聚糖均显著降低。在糖基转移酶水平上，用多种技术包括实时PCR、蛋白质印迹、transwell测定、凝集素印迹和免疫组织化学分析进一步验证了等分GlcNAc糖型的这种改变及其与卵巢癌转移行为的相应关联。这项研究首次在体外阐明了卵巢癌分泌组中与转移相关的N-聚糖改变，这也是生物标志物发现的有价值的来源。此外，N-聚糖与二等分GlcNAc有助于卵巢癌早期腹膜转移的检测，从而改善卵巢癌患者的预后。
Generally, most of ovarian cancer cannot be detected until large scale and remote metastasis occurs, which is the major cause of high mortality in ovarian cancer. Therefore, it is urgent to discover metastasis-related biomarkers for the detection of ovarian cancer in its occult metastasis stage. Altered glycosylation is a universal feature of malignancy and certain types of glycan structures are well-known markers for tumor progressions. Thus, this study aimed to reveal specific changes of N-glycans in the secretome of the metastatic ovarian cancer. We employed a quantitative glycomics approach based on metabolic stable isotope labeling to compare the differential N-glycosylation of secretome between an ovarian cancer cell line SKOV3 and its high metastatic derivative SKOV3-ip. Intriguingly, among total 17 N-glycans identified, the N-glycans with bisecting GlcNAc were all significantly decreased in SKOV3-ip in comparison to SKOV3. This alteration in bisecting GlcNAc glycoforms as well as its corresponding association with ovarian cancer metastatic behavior was further validated at the glycotransferase level with multiple techniques including real-time PCR, western blotting, transwell assay, lectin blotting and immunohistochemistry analysis. This study illustrated metastasis-related N-glycan alterations in ovarian cancer secretome in vitro for the first time, which is a valuable source for biomarker discovery as well. Moreover, N-glycans with bisecting GlcNAc shed light on the detection of ovarian cancer in early peritoneal metastasis stage which may accordingly improve the prognosis of ovarian cancer patients.
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影响因子：
3.4
作者：
Abbott KL;Lim JM;Wells L;Benigno BB;McDonald JF;Pierce M
通讯作者：
Pierce M
影响因子：
11.5
作者：
Handerson, T;Camp, R;Pawelek, J
通讯作者：
Pawelek, J
影响因子：
4
作者：
Casey, RC;Oegema, TR;Skubitz, APN
通讯作者：
Skubitz, APN
影响因子：
2.7
作者：
GU, JG;NISHIKAWA, A;TANIGUCHI, N
通讯作者：
TANIGUCHI, N
影响因子：
4.3
作者：
Gu, JG;Zhao, YY;Taniguchi, N
通讯作者：
Taniguchi, N