title: Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients.
abstract: OBJECTIVE
  Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women.
  
  
  METHODS
  FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate.
  
  
  RESULTS
  FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P<0.0001) and patients with benign gynecological conditions (P<0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125.
  
  
  CONCLUSIONS
  FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Leung
authors.forename: A
authors.initials: A
authors.lastname: Dimitromanolakis
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: E P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: V
authors.initials: V
authors.lastname: Kulasingam
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018394:CA-125 Antigen / Q000097:blood / Q000235:genetics*; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D018925:Chemokines; D005260:Female; D058975:Folate Receptor 1 / Q000097:blood / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018925:Chemokines; C498624:DKK3 protein, human; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D036341:Intercellular Signaling Peptides and Proteins; C451759:MUC16 protein, human; D008565:Membrane Proteins
keywords: AUC; Biomarker; CA125; CI; Diagnostic; Dickkopf-related protein 3; Dkk-3; ELISA; FDA; FOLR1; Food and Drug Administration; NID2; OR; Ovarian cancer; ROC; ROMA; Risk of Malignancy Algorithm; area under the curve; carbohydrate antigen 125; confidence interval; enzyme-linked immunosorbent assay; folate-receptor 1; nidogen-2; odds ratio; receiver operating characteristic