Alterations in the Serum Glycome Due to ... - ACS Publications

Dec 12, 2006 - Principal component analysis of the glycomic profiles revealed significant .... clinical trial conducted through the Hoosier Oncology G...
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Alterations in the Serum Glycome Due to Metastatic Prostate Cancer Zuzana Kyselova,† Yehia Mechref,*,† Mohammad M. Al Bataineh,† Lacey E. Dobrolecki,‡ Robert J. Hickey,‡ Jake Vinson,§ Christopher J. Sweeney,‡ and Milos V. Novotny*,†,‡ National Center for Glycomics and Glycoproteomics, Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, and Hoosier Oncology Group, LLC, Indianapolis, Indiana 46202

Received December 12, 2006

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-µL 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 (