Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples.

Abstract

An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response.

• Authors: Elizabeth S Hecht, Elizabeth H Scholl, S Hunter Walker, Amber D Taylor, William A Cliby, Alison A Motsinger-Reif, David C Muddiman
• Journal: Journal of proteome research (J Proteome Res) Vol. 14 Issue 10 Pg. 4394-401 (Oct 02 2015) ISSN: 1535-3907 [Electronic] United States
• PMID: 26347193 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Hydrazines
• Polysaccharides
• Sialic Acids
• Fucose

Topics

• Biomarkers, Tumor (blood)
• Carbohydrate Sequence
• Case-Control Studies
• Chromatography, Liquid (methods)
• Female
• Fucose (blood)
• Glycosylation
• Humans
• Hydrazines (chemistry)
• Molecular Sequence Data
• Neoplasm Staging
• Ovarian Neoplasms (blood, diagnosis, pathology)
• Polysaccharides (blood)
• Sialic Acids (blood)
• Staining and Labeling (methods)
• Tandem Mass Spectrometry (methods)