Identification of Differential N-Glycan Compositions in the Serum and Tissue of Colon Cancer Patients by Mass Spectrometry.
Identification of Differential N-Glycan Compositions in the Serum and Tissue of Colon Cancer Patients by Mass Spectrometry.
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DOI：
10.3390/biology10040343
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发表时间：
2021-04-20
期刊：
影响因子：
4.2
通讯作者：
de Sousa JB
中科院分区：
文献类型：
--
作者：
Coura MMA;Barbosa EA;Brand GD;Bloch C Jr;de Sousa JB
在巴西，结直肠癌（CRC）的发病率一直在上升。迄今为止，没有可靠的生物标志物已被描述在CRC的诊断和预后。N-糖基化谱的修饰通常与许多癌症相关，如CRC。反过来，基于质谱（MS）的方法是定量N-聚糖的最准确技术。因此，我们描述了一种独特的模式，改变了II期和III期结肠癌患者的血清和组织中的组合物，确定了MALDI-TOF/MS和LC-MS技术。N-聚糖主要在血清中减少，而寡甘露糖苷、低半乳糖基化和四触角形式在肿瘤组织中过表达。癌症患者血清中的总N-糖组与健康个体血清中发现的谱不同。令人惊讶的是，在癌症患者中没有观察到组织N-糖基化谱和血清谱之间的相关性，提出了这些组合物来源于何处的问题。结直肠癌（CRC）是全球癌症相关死亡的第二大原因。N-糖基化是最常见的蛋白质翻译后修饰之一。因此，我们使用MALDI-TOF/MS和LC-MS研究了与健康对照相比的13名结肠癌患者的总血清N-糖基化（TSNG）。使用类似的方法进一步定量来自同一队列的癌症肿瘤样品的N-糖基化。总之，结肠癌患者血清中23种N-聚糖组分下调，主要是半乳糖基化形式，而富含甘露糖的HexNAc 2 Hex 7、岩藻糖基化双触角聚糖HexNAc 4 Hex 5 Fuc 1 NeuAc 2和四触角HexNAc 6 Hex 7 NeuAc 3在血清中上调。TSNG的层次聚类分析正确地从对照组中选出了85%的患者。尽管肿瘤样本的N-糖基化是异质的，但在MALDI-TOF/MS和LC-MS分析中，与正常结肠组织相关的寡甘露糖苷、双触角低半乳糖基化和分支组成过多。此外，在肿瘤组织中发现上调的组合物大多与癌症患者血清中的组合物不相关。血清中基于质谱的N-聚糖谱显示出区分患者与健康对照的潜力。然而，血清中的组合物谱显示与肿瘤微环境中的N-聚糖不平行，这表明在癌症患者血清中发现的组合物的不同来源。
Incidence of colorectal cancer (CRC) has been rising in Brazil. To date, no reliable biomarker has been described in CRC for diagnosis and prognosis. Modifications in the N-glycosylation profile are usually associated with many cancers, as CRC. In turn, mass spectrometry (MS)-based methods are the most accurate technology in quantification of N-glycans. Therefore, we described a unique pattern of compositions altered in serum and tissues of stages II and III colon cancer patients, identified by MALDI-TOF/MS and LC-MS technology. N-glycans were mostly found decreased in serum whilst oligomannosidic, hypogalactosylated, and tetra-antennary forms were overexpressed in tumor tissues. Total N-glycome in serum of cancer patients was different from the profile found in serum of healthy individuals. Strikingly, no correlation between tissue N-glycosylation profile and serum profile was observed in cancer patients, posing the question where these compositions are originated from. Colorectal cancer (CRC) ranks second as the leading cause of cancer-related deaths worldwide. N-glycosylation is one of the most common posttranslational protein modifications. Therefore, we studied the total serum N-glycome (TSNG) of 13 colon cancer patients compared to healthy controls using MALDI-TOF/MS and LC-MS. N-glycosylation of cancer tumor samples from the same cohort were further quantified using a similar methodology. In total, 23 N-glycan compositions were down-regulated in the serum of colon cancer patients, mostly galactosylated forms whilst the mannose-rich HexNAc2Hex7, the fucosylated bi-antennary glycan HexNAc4Hex5Fuc1NeuAc2, and the tetra-antennary HexNAc6Hex7NeuAc3 were up-regulated in serum. Hierarchical clustering analysis of TSNG correctly singled out 85% of the patients from controls. Albeit heterogenous, N-glycosylation of tumor samples showed overrepresented oligomannosidic, bi-antennary hypogalactosylated, and branched compositions related to normal colonic tissue, in both MALDI-TOF/MS and LC-MS analysis. Moreover, compositions found upregulated in tumor tissue were mostly uncorrelated to compositions in serum of cancer patients. Mass spectrometry-based N-glycan profiling in serum shows potential in the discrimination of patients from healthy controls. However, the compositions profile in serum showed no parallel with N-glycans in tumor microenvironment, which suggests a different origin of compositions found in serum of cancer patients.
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影响因子：
4.6
作者：
Doherty M;Theodoratou E;Walsh I;Adamczyk B;Stöckmann H;Agakov F;Timofeeva M;Trbojević-Akmačić I;Vučković F;Duffy F;McManus CA;Farrington SM;Dunlop MG;Perola M;Lauc G;Campbell H;Rudd PM
通讯作者：
Rudd PM
影响因子：
29.4
作者：
Clerc, Florent;Novokmet, Mislav;Wuhrer, Manfred
通讯作者：
Wuhrer, Manfred
影响因子：
--
作者：
de Vroome SW;Holst S;Girondo MR;van der Burgt YEM;Mesker WE;Tollenaar RAEM;Wuhrer M
通讯作者：
Wuhrer M
影响因子：
2.9
作者：
Hu, Yunli;Mechref, Yehia
通讯作者：
Mechref, Yehia
DOI：
10.1074/mcp.m111.011601
发表时间：
2012-09
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Balog CI;Stavenhagen K;Fung WL;Koeleman CA;McDonnell LA;Verhoeven A;Mesker WE;Tollenaar RA;Deelder AM;Wuhrer M
通讯作者：
Wuhrer M