Alterations in the serum glycome due to metastatic prostate cancer
Alterations in the serum glycome due to metastatic prostate cancer
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DOI：
10.1021/pr060664t
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Novotny, Milos V.
中科院分区：
文献类型：
--
作者：
Kyselova, Zuzana;Mechref, Yehia;Novotny, Milos V.
将来自10名健康男性的人血清的糖组学谱与来自24名前列腺癌患者的糖组学谱进行比较。使用从10 μ L样品等分试样中释放的全甲基化N-聚糖的MALDI-MS获得图谱。使用固相全甲基化实现定量全甲基化。主成分分析的糖谱显示显着差异，这两组，使其不同的聚类。第一主成分区分24例前列腺癌患者和健康个体。确定聚糖结构的岩藻糖基化在癌症样品中通常较高（ANOVA检验p值为0.0006）。虽然测定了50多种N-聚糖结构，但两个样品组之间有12种聚糖结构（其中6种为岩藻糖基化）存在显著差异。通过两个独立的统计检验（ANOVA和ROC分析）证实了显著差异。在癌症样本中，这些结构中的10个具有显著更高的相对强度，而另外两个在癌症样本中的丰度较低。所有12个结构都具有统计学显著性，如其非常低的ANOVA评分（< 0.001）和ROC分析所示，曲线下面积值接近1或0。因此，这些结构可以被认为是癌症特异性聚糖和潜在的前列腺癌生物标志物。因此，血清糖组学分析值得进一步研究，以确定其在癌症早期检测和诊断中的作用。关键词：前列腺癌中心点糖组学中心点人血清中心点生物标志物中心点MALDI-TOF中心点质谱
Glycomic profiles derived from human blood sera of 10 healthy males were compared to those from 24 prostate cancer patients. The profiles were acquired using MALDI-MS of permethylated N-glycans released from 10-mu L sample aliquots. Quantitative permethylation was attained using solid-phase permethylation. Principal component analysis of the glycomic profiles revealed significant differences among the two sets, allowing their distinct clustering. The first principal component distinguished the 24 prostate cancer patients from the healthy individuals. It was determined that fucosylation of glycan structures is generally higher in cancer samples (ANOVA test p-value of 0.0006). Although more than 50 N-glycan structures were determined, 12 glycan structures, of which six were fucosylated, were significantly different between the two sample sets. Significant differences were confirmed through two independent statistical tests (ANOVA and ROC analyses). Ten of these structures had significantly higher relative intensities in the case of the cancer samples, while the other two were less abundant in the cancer samples. All 12 structures were statistically significant, as suggested by their very low ANOVA scores (< 0.001) and ROC analysis, with area under the curve values close to 1 or 0. Accordingly, these structures can be considered as cancer-specific glycans and potential prostate cancer biomarkers. Therefore, serum glycomic profiling appears worthy of further investigation to define its role in cancer early detection and prognostication.Keywords: prostate cancer center dot glycomics center dot human blood serum center dot biomarkers center dot MALDI-TOF center dot mass spectrometry