title: Validation of a Novel Biomarker Panel for the Detection of Ovarian Cancer.
abstract: Ovarian cancer is the most lethal gynecological malignancy. Our integrated -omics approach to ovarian cancer biomarker discovery has identified kallikrein 6 (KLK6) and folate-receptor 1 (FOLR1) as promising candidates but these markers require further validation.
  
  
  
  KLK6, FOLR1, CA125, and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls, and 216 ovarian cancer patients. The serum biomarker levels were determined by ELISA or automated immunoassay.
  
  
  
  All biomarkers demonstrated elevations in the sera of ovarian cancer patients compared with controls (P < 0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify ovarian cancer patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. In addition, the combination of HE4 and FOLR1 was a strong predictor of ovarian cancer diagnosis, displaying comparable sensitivity (65%) to the best-performing CA125-based models (67%) at a set specificity of 95%.
  
  
  
  The markers identified through our integrated -omics approach performed similarly to the clinically approved markers CA125 and HE4. Furthermore, HE4 represents a powerful diagnostic marker for ovarian cancer and should be used more routinely in a clinical setting.
  
  
  
  The implications of our study are 2-fold: (i) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (ii) we have demonstrated the clinical utility of our integrated -omics approach to identifying novel serum markers with comparable performance to clinical markers. Cancer Epidemiol Biomarkers Prev; 25(9); 1333-40. ©2016 AACR.
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: Felix
authors.initials: F
authors.lastname: Leung
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marcus Q
authors.initials: MQ
authors.lastname: Bernardini
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Marshall D
authors.initials: MD
authors.lastname: Brown
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yingye
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Service of Clinical Biochemistry, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Molina
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.affiliation: Abbott Diagnostics, Lake Forest, Illinois.
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.affiliation: Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
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. Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada. vathany.kulasingam@uhn.ca.
authors.forename: Vathany
authors.initials: V
authors.lastname: Kulasingam
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058975:Folate Receptor 1 / Q000097:blood*; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D011506:Proteins / Q000032:analysis*; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins