Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples.
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.
Elizabeth S
ES
Hecht
Elizabeth H
EH
Scholl
S Hunter
SH
Walker
Amber D
AD
Taylor
Division of Gynecologic Surgery, Mayo Clinic , Rochester, Minnesota 55905, United States.
William A
WA
Cliby
Alison A
AA
Motsinger-Reif
David C
DC
Muddiman
D014408:Biomarkers, Tumor / Q000097:blood*; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D005643:Fucose / Q000097:blood; D006031:Glycosylation; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011134:Polysaccharides / Q000097:blood*; D012794:Sialic Acids / Q000097:blood; D013194:Staining and Labeling / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D014408:Biomarkers, Tumor; D006834:Hydrazines; D011134:Polysaccharides; D012794:Sialic Acids; D005643:Fucose
INLIGHT; N-linked glycosylation; cancer biomarker; human plasma; ovarian cancer; relative quantification