title: A Nanoparticle-Lectin Immunoassay Improves Discrimination of Serum CA125 from Malignant and Benign Sources.
abstract: Measurement of serum cancer antigen 125 (CA125) is the standard approach for epithelial ovarian cancer (EOC) diagnostics and follow-up. However, the clinical specificity is not optimal because increased values are also detected in healthy controls and in benign diseases. CA125 is known to be differentially glycosylated in EOC, potentially offering a way to construct CA125 assays with improved cancer specificity. Our goal was to identify carbohydrate-reactive lectins for discriminating between CA125 originating from EOC and noncancerous sources.
  
  
  
  CA125 from the OVCAR-3 cancer cell line, placental homogenate, and ascites fluid from patients with cirrhosis were captured on anti-CA125 antibody immobilized on microtitration wells. A panel of lectins, each coated onto fluorescent europium-chelate-doped 97-nm nanoparticles (Eu(+3)-NPs), was tested for detection of the immobilized CA125. Serum samples from high-grade serous EOC or patients with endometriosis and healthy controls were analyzed.
  
  
  
  By using macrophage galactose-type lectin (MGL)-coated Eu(+3)-NPs, an analytically sensitive CA125 assay (CA125(MGL)) was achieved that specifically recognized the CA125 isoform produced by EOC, whereas the recognition of CA125 from nonmalignant conditions was reduced. Serum CA125(MGL) measurement better discriminated patients with EOC from endometriosis compared to conventional immunoassay. The discrimination was particularly improved for marginally increased CA125 values and for earlier detection of EOC progression.
  
  
  
  The new CA125(MGL) assay concept could help reduce the false-positive rates of conventional CA125 immunoassays. The improved analytical specificity of this test approach is dependent on a discriminating lectin immobilized in large numbers on Eu(+3)-NPs, providing both an avidity effect and signal amplification.
authors.affiliation: Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland; kamgid@utu.fi.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Gidwani
authors.affiliation: Department of Pathology, Medicity research laboratories, University of Turku and Turku University Hospital, Turku, Finland;
authors.forename: Kaisa
authors.initials: K
authors.lastname: Huhtinen
authors.affiliation: Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland;
authors.forename: Henna
authors.initials: H
authors.lastname: Kekki
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Sandra
authors.initials: S
authors.lastname: van Vliet
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland;
authors.forename: Johanna
authors.initials: J
authors.lastname: Hynninen
authors.affiliation: Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland;
authors.forename: Niina
authors.initials: N
authors.lastname: Koivuviita
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland;
authors.forename: Antti
authors.initials: A
authors.lastname: Perheentupa
authors.affiliation: Department of Physiology, Institute of Biomedicine, and Turku Center for Disease Modeling, University of Turku, Finland;
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland; Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland;
authors.forename: Annika
authors.initials: A
authors.lastname: Auranen
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland;
authors.forename: Seija
authors.initials: S
authors.lastname: Grenman
authors.affiliation: Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland;
authors.forename: Urpo
authors.initials: U
authors.lastname: Lamminmäki
authors.affiliation: Department of Pathology, Medicity research laboratories, University of Turku and Turku University Hospital, Turku, Finland; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Carpen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.affiliation: Department of Biochemistry/Biotechnology, University of Turku, Turku, Finland;
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry; D018394:CA-125 Antigen / Q000097:blood* / Q000737:chemistry; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D037102:Lectins / Q000737:chemistry*; D008875:Middle Aged; D053758:Nanoparticles / Q000737:chemistry*; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D037102:Lectins