Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array

Int J Cancer. 2012 Jan 1;130(1):138-46. doi: 10.1002/ijc.26002. Epub 2011 Apr 25.

Abstract

Epithelial ovarian cancer has the highest mortality rate among gynecological cancers. Altered glycosylation is associated with oncogenic transformation producing tumor-associated carbohydrate antigens. We investigated the potential of natural occurring antiglycan antibodies in the diagnosis of ovarian cancer by using printed glycan array. Antiglycan antibodies bound to 203 chemically synthesized printed glycans were detected via biotin-streptavidin fluorescence system in serum of women with normal operative findings (healthy controls; n = 24) and nonmucinous borderline or ovarian cancer of various FIGO stages (n = 33). Data were validated measuring blood group associated di-, tri and tetrasaccharide antigens on known ABO blood groups. Antiglycan antibodies demonstrated high reproducibility (r(c) > 0.9). Cluster analysis identified repetitive patterns of specific core carbohydrate structures: 11 N-linked glycans, 3 O-linked glycans and 2 glycosphingolipids. Biomarker detection revealed 24 glycans including P(1) (Galα1-4Galβ1-4GlcNAcβ; p < 0.001) significantly discriminating between (low-) malignant tumors and healthy controls. Comparable sensitivity and specificity with tumor marker CA125 was achieved by a panel of multivariate selected and linear combined antiglycan antibody signals (79.2 and 84.8%, respectively). Our findings demonstrate the potential of glycan arrays in the development of a new generation of biomarkers for ovarian cancer.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / immunology
  • Adenocarcinoma, Clear Cell / metabolism
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Transitional Cell / immunology
  • Carcinoma, Transitional Cell / metabolism
  • Case-Control Studies
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / metabolism
  • Endometrial Neoplasms / immunology
  • Endometrial Neoplasms / metabolism
  • Female
  • Follow-Up Studies
  • Glycosylation
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology*
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism*
  • Polysaccharides / analysis*
  • Polysaccharides / blood
  • Polysaccharides / immunology*
  • Prognosis
  • Prospective Studies
  • Proteomics

Substances

  • Biomarkers, Tumor
  • Immunoglobulin G
  • Polysaccharides