title: Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array.
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.
authors.affiliation: Translational Research Group, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Francis
authors.initials: F
authors.lastname: Jacob
authors.forename: Darlene R
authors.initials: DR
authors.lastname: Goldstein
authors.forename: Nicolai V
authors.initials: NV
authors.lastname: Bovin
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pochechueva
authors.forename: Marianne
authors.initials: M
authors.lastname: Spengler
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Caduff
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.forename: Marko I
authors.initials: MI
authors.lastname: Vuskovic
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Huflejt
authors.forename: Viola
authors.initials: V
authors.lastname: Heinzelmann-Schwarz
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000276:immunology / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000276:immunology / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000276:immunology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D046228:Microarray Analysis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism*; D011134:Polysaccharides / Q000032:analysis* / Q000097:blood / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics
chemical_list: D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D011134:Polysaccharides