A serum glycomics approach to breast cancer biomarkers
A serum glycomics approach to breast cancer biomarkers
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DOI：
10.1074/mcp.m600171-mcp200
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发表时间：
2007-01-01
影响因子：
7
通讯作者：
Miyamoto, Suzanne
中科院分区：
文献类型：
--
作者：
Kirmiz, Crystal;Li, Bensheng;Miyamoto, Suzanne
由于已知蛋白质的糖基化在乳腺癌发生发展的过程中会在肿瘤细胞中发生变化，因此这里使用糖组学方法来寻找乳腺癌的相关生物标志物。已知这些糖基化改变与肿瘤负担增加和预后不良有关。目前卵巢癌(CA125)、乳腺癌(CA27.29或CA15-3)、胰腺癌、胃癌、结肠癌和癌(CA19-9)等癌症生物标志物的基于抗体的免疫化学检测以高度糖基化的粘蛋白为目标。然而，这些检测缺乏用于早期检测的特异性和敏感性。这种寻找乳腺癌糖链生物标记物的糖组学方法涉及从乳腺癌细胞系脱落或分泌的糖基化蛋白中化学裂解寡糖(糖链)。利用MALDI-FT-ICR MS对所得的游离多糖物种进行了分析，并通过红外多光子解离串联质谱仪对这些多糖进行了进一步的结构分析。为每种细胞系生成糖链图谱并进行比较。然后，这些方法被用来分析从乳腺癌小鼠模型中获得的血清，以及从被诊断为乳腺癌的人类患者或没有已知乳腺癌病史的患者那里获得的少量血清样本。除了在小鼠乳腺肿瘤发生时在小鼠身上检测到的糖基化变化外，还发现糖基化特征有很大的不同，足以区分癌症患者和非癌症患者。尽管到目前为止分析的少量患者样本不足以在这个时候做出任何合法的声明，但这些有希望但非常初步的结果表明，糖链图谱可能包含不同的糖链生物标记物，这些生物标记物可能对应于葡聚糖“癌症的特征”。
Because the glycosylation of proteins is known to change in tumor cells during the development of breast cancer, a glycomics approach is used here to find relevant biomarkers of breast cancer. These glycosylation changes are known to correlate with increasing tumor burden and poor prognosis. Current antibody-based immunochemical tests for cancer biomarkers of ovarian (CA125), breast (CA27.29 or CA15-3), pancreatic, gastric, colonic, and carcinoma (CA19-9) target highly glycosylated mucin proteins. However, these tests lack the specificity and sensitivity for use in early detection. This glycomics approach to find glycan biomarkers of breast cancer involves chemically cleaving oligosaccharides (glycans) from glycosylated proteins that are shed or secreted by breast cancer tumor cell lines. The resulting free glycan species are analyzed by MALDI-FT-ICR MS. Further structural analysis of the glycans can be performed in FTMS through the use of tandem mass spectrometry with infrared multiphoton dissociation. Glycan profiles were generated for each cell line and compared. These methods were then used to analyze sera obtained from a mouse model of breast cancer and a small number of serum samples obtained from human patients diagnosed with breast cancer or patients with no known history of breast cancer. In addition to the glycosylation changes detected in mice as mouse mammary tumors developed, glycosylation profiles were found to be sufficiently different to distinguish patients with cancer from those without. Although the small number of patient samples analyzed so far is inadequate to make any legitimate claims at this time, these promising but very preliminary results suggest that glycan profiles may contain distinct glycan biomarkers that may correspond to glycan "signatures of cancer.".