Alterations in the serum glycome due to metastatic prostate cancer.
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-microL 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.
Kyselova
Zuzana
Z
National Center for Glycomics and Glycoproteomics, Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405, USA.
Mechref
Yehia
Y
Al Bataineh
Mohammad M
MM
Dobrolecki
Lacey E
LE
Hickey
Robert J
RJ
Vinson
Jake
J
Sweeney
Christopher J
CJ
Novotny
Milos V
MV
D019540:Area Under Curve; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011134:Polysaccharides / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001798:Blood Proteins; D006023:Glycoproteins; D011134:Polysaccharides