Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients

PLoS One. 2016 Oct 20;11(10):e0164230. doi: 10.1371/journal.pone.0164230. eCollection 2016.

Abstract

Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2-6 vs. α2-3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers.

MeSH terms

  • Aged
  • Antibodies / blood*
  • Antibodies / immunology
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • CA-125 Antigen / blood
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Grading
  • Neuraminic Acids / chemistry
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • ROC Curve
  • Sulfates / chemistry

Substances

  • Antibodies
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Neuraminic Acids
  • Polysaccharides
  • Sulfates

Grant support

This work was supported by Cancer Institute NSW, 09/CRF/2-02; RANZCOG Research Foundation; William Maxwell Trust; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, 310030-156982; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, 310030_143619; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, 310030_143632; Oncosuisse, KFS_3013-08-2012; Krebsliga Beider Basel, 06-2013; and Russian Science Foundation, 14-50-00131. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.