title: Multicenter study identified molecular blood-born protein signatures for Wilms Tumor.
abstract: Wilms Tumor (WT) is the most common renal childhood tumor. Recently, we reported a cDNA microarray expression pattern that varied between WTs with different risk histology. Since the Societé Internationale d'Oncologie Pédiatrique (SIOP) in Europe initiates treatment without a histological confirmation, it is important to identify blood-born markers that indicate WT development. In a multicenter study, we established an autoantibody signature by using an array with 1,827 recombinant E. coli clones. This array was screened with sera of patients with WT recruited by SIOP or the Children's Oncology Group (COG). We report an extended number of antigens that are reactive with autoantibodies present in sera from patients with WT. We established an autoantibody signature that separates untreated patients with WT recruited in SIOP from non-WT controls with a specificity of 0.83 and a sensitivity of 0.82 at standard deviations of 0.02 and 0.04, respectively. Likewise, patients recruited in the COG in the United States were separated from the controls with an accuracy of 0.83 at a standard deviation of 0.02. Proteins that were most significant include zinc finger proteins (e.g., ZFP 346), ribosomal proteins and the protein fascin that has been associated with various types of cancer including renal cell carcinoma. Our study provides first evidence for autoantibody signatures for WTs and suggests that these may be most informative before chemotherapy. We present the first multicenter study of autoantibody signatures in patients with WT. We established an autoantibody signature that separates patients with WT from controls.
authors.affiliation: Department of Human Genetics, Medical School, Saarland University, 66421 Homburg, Germany. jana.schmitt@uniklinikum-saarland.de
authors.forename: Jana
authors.initials: J
authors.lastname: Schmitt
authors.forename: Sabrina
authors.initials: S
authors.lastname: Heisel
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.forename: Nicole
authors.initials: N
authors.lastname: Ludwig
authors.forename: Nunja
authors.initials: N
authors.lastname: Habel
authors.forename: Rhoikos
authors.initials: R
authors.lastname: Furtwängler
authors.forename: Nasenien
authors.initials: N
authors.lastname: Nourkami-Tutdibi
authors.forename: Jenny
authors.initials: J
authors.lastname: Wegert
authors.forename: Paul
authors.initials: P
authors.lastname: Grundy
authors.forename: Manfred
authors.initials: M
authors.lastname: Gessler
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lenhof
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
mesh_terms: D000293:Adolescent; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood; D002352:Carrier Proteins / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008840:Microfilament Proteins / Q000097:blood* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D016601:RNA-Binding Proteins / Q000097:blood* / Q000276:immunology; D012269:Ribosomal Proteins / Q000097:blood* / Q000276:immunology; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C121935:ZNF346 protein, human; C020324:fascin