TY - JOUR
T1 - Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples
AU - Hecht, Elizabeth S.
AU - Scholl, Elizabeth H.
AU - Walker, S. Hunter
AU - Taylor, Amber D.
AU - Cliby, William A.
AU - Motsinger-Reif, Alison A.
AU - Muddiman, David C.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/10/2
Y1 - 2015/10/2
N2 - 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.
AB - 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.
KW - INLIGHT
KW - N-linked glycosylation
KW - cancer biomarker
KW - human plasma
KW - ovarian cancer
KW - relative quantification
UR - http://www.scopus.com/inward/record.url?scp=84942861116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942861116&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.5b00703
DO - 10.1021/acs.jproteome.5b00703
M3 - Article
C2 - 26347193
AN - SCOPUS:84942861116
SN - 1535-3893
VL - 14
SP - 4394
EP - 4401
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 10
ER -