Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers.
Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers.
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DOI：
10.1021/pr201206w
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发表时间：
2012-04-06
影响因子：
4.4
通讯作者：
Fisher SJ
中科院分区：
文献类型：
--
作者：
Drake PM;Schilling B;Niles RK;Prakobphol A;Li B;Jung K;Cho W;Braten M;Inerowicz HD;Williams K;Albertolle M;Held JM;Iacovides D;Sorensen DJ;Griffith OL;Johansen E;Zawadzka AM;Cusack MP;Allen S;Gormley M;Hall SC;Witkowska HE;Gray JW;Regnier F;Gibson BW;Fisher SJ
我们使用凝集素层析/MS方法从一组腔(侵袭性较弱)和三重阴性(侵袭性较强)乳腺癌细胞系(n=5/亚型)中筛选条件培养液。样品用分别识别岩藻糖和唾液酸的凝集素橙花(AAL)和接骨木凝集素(SNA)进行分级。结合组分经N-脱糖处理后，经LC-MS/MS分析，共鉴定出533种糖蛋白，其中约90%为细胞表面或细胞外基质成分。我们观察到1011个糖位，其中100个仅在≥-3三重阴性线上检测到。统计分析表明，这些糖点中的许多是三重阴性特异性的，因此可能是该肿瘤亚型的生物标记物。对RNAseq数据的分析显示，编码携带潜在生物标记物糖位的蛋白质支架的mRNAs中，大约有一半在三阴性细胞系和腔细胞系中上调，并且一些编码岩藻糖基或唾液酸基转移酶的基因在这两种亚型之间存在差异表达，这表明糖基化的变化也可能推动候选识别。值得注意的是，这些假定的生物标志物候选的糖蛋白参与了与癌症相关的过程。因此，它们可能是这种侵袭性肿瘤亚型的新的治疗靶点。
We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n = 5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ~90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in ≥3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNAseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were upregulated in triple negative vs. luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype.
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影响因子：
3
作者：
Akasaka-Manya, Keiko;Manya, Hiroshi;Endo, Tamao
通讯作者：
Endo, Tamao
影响因子：
4.8
作者：
Garrigue-Antar, L;Hartigan, N;Kadler, KE
通讯作者：
Kadler, KE
影响因子：
2
作者：
Bast, RC;Xu, FJ;Mills, GB
通讯作者：
Mills, GB
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
56.9
作者：
Bergers, G;Javaherian, K;Hanahan, D
通讯作者：
Hanahan, D