title: Plasma bikunin as a favorable prognostic factor in ovarian cancer.
abstract: OBJECTIVE
  Bikunin is a multifunctional glycoprotein, which mediates suppression of tumor cell invasion and metastasis. The measurement of bikunin levels in the tissue of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the evaluation of prognosis. The high bikunin expression in ovarian cancer tissue would enable the use of soluble bikunin protein present in the circulation of ovarian cancer patients as a biomarker of disease.
  
  
  METHODS
  We developed a double-antibody immunoassay for bikunin and detected its presence in normal human circulation. We quantified, by enzyme-linked immunosorbent assay and/or immunoblot assay bikunin in sera from 200 healthy women (controls), 200 patients with benign gynecologic diseases, and 327 patients with ovarian cancer before surgical removal of the tumor.
  
  
  RESULTS
  When the values of bikunin corresponding to the median were used as the cutoff value (11.5 microg/mL), low plasma bikunin was strongly associated with late-stage, suboptimal debulking with large residual tumor (> 2 cm) and low response to chemotherapy. The median survival time of the patients with a high bikunin level was more than 60 months as compared with 26 months among those with low bikunin level (P = .002). This difference corresponded to a 2.2-fold increased risk of dying for the lower plasma bikunin patients (hazard ratio, 0.45; P = .023) and remained significant in multivariate analysis (hazard ratio, 0.63; P = .041).
  
  
  CONCLUSIONS
  Preoperative plasma bikunin concentration is a strong and independent favorable prognostic marker for ovarian cancer.
authors.affiliation: Netforce Co Ltd., Nakamura, Aichi, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yagyu
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Wakahara
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kondo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurita
authors.forename: Hideo
authors.initials: H
authors.lastname: Sekino
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Inagaki
authors.forename: Mika
authors.initials: M
authors.lastname: Suzuki
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kanayama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Terao
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D004309:Double Bind Interaction; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005831:Genital Diseases, Female / Q000097:blood; D006801:Humans; D007118:Immunoassay; D008562:Membrane Glycoproteins / Q000097:blood*; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000097:blood / Q000401:mortality* / Q000601:surgery; D011379:Prognosis; D012372:ROC Curve; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D014360:Trypsin Inhibitor, Kunitz Soybean