title: Autoantibody signature for the serologic detection of ovarian cancer.
abstract: Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p < 0.01). Using a panel of the top three AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, then the sensitivity was 23.3% at 98.3% specificity. AAb to at least one of these top three antigens were also detected in 7/20 sera (35%) of patients with low CA 125 levels and 0/15 controls. AAb to p53, PTPRA, and PTGFR are potential biomarkers for the early detection of ovarian cancer.
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University , Tempe, Arizona 85287-6401, United States.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
authors.forename: Sahar
authors.initials: S
authors.lastname: Sibani
authors.forename: Garrick
authors.initials: G
authors.lastname: Wallstrom
authors.forename: Jessica
authors.initials: J
authors.lastname: Wong
authors.forename: Jin
authors.initials: J
authors.lastname: Park
authors.forename: Ji
authors.initials: J
authors.lastname: Qiu
authors.forename: Allison
authors.initials: A
authors.lastname: Vitonis
authors.forename: Joshua
authors.initials: J
authors.lastname: LaBaer
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D012044:Regression Analysis; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G
keywords: Ovarian cancer; autoantibodies; biomarker; protein microarrays; proteomics