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

Elizabeth S. Hecht, Elizabeth H. Scholl, S. Hunter Walker, Amber D. Taylor, William Arthur Cliby, Alison A. Motsinger-Reif, David C. Muddiman

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4394-4401
Number of pages8
JournalJournal of Proteome Research
Volume14
Issue number10
DOIs
StatePublished - Oct 2 2015

Keywords

  • cancer biomarker
  • human plasma
  • INLIGHT
  • N-linked glycosylation
  • ovarian cancer
  • relative quantification

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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