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

Journal of Proteome Research
Elizabeth S HechtDavid C Muddiman

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, t...Continue Reading

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Citations

Sep 4, 2016·Analytical and Bioanalytical Chemistry·Muchena J KailemiaCarlito B Lebrilla
Jul 7, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Huanhuan ChenYan Li
Oct 28, 2018·Proteomics. Clinical Applications·Matthew T BriggsPeter Hoffmann
Nov 14, 2019·Current Protocols in Protein Science·Alyson P BlackAnand S Mehta
Mar 9, 2017·Analytical and Bioanalytical Chemistry·Clemens Grünwald-GruberFriedrich Altmann
Mar 20, 2018·Chemical Reviews·L Renee RuhaakCarlito B Lebrilla

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