title: A combined blood based gene expression and plasma protein abundance signature for diagnosis of epithelial ovarian cancer--a study of the OVCAD consortium.
abstract: BACKGROUND
  The immune system is a key player in fighting cancer. Thus, we sought to identify a molecular 'immune response signature' indicating the presence of epithelial ovarian cancer (EOC) and to combine this with a serum protein biomarker panel to increase the specificity and sensitivity for earlier detection of EOC.
  
  
  METHODS
  Comparing the expression of 32,000 genes in a leukocytes fraction from 44 EOC patients and 19 controls, three uncorrelated shrunken centroid models were selected, comprised of 7, 14, and 6 genes. A second selection step using RT-qPCR data and significance analysis of microarrays yielded 13 genes (AP2A1, B4GALT1, C1orf63, CCR2, CFP, DIS3, NEAT1, NOXA1, OSM, PAPOLG, PRIC285, ZNF419, and BC037918) which were finally used in 343 samples (90 healthy, six cystadenoma, eight low malignant potential tumor, 19 FIGO I/II, and 220 FIGO III/IV EOC patients). Using new 65 controls and 224 EOC patients (thereof 14 FIGO I/II) the abundances of six plasma proteins (MIF, prolactin, CA125, leptin, osteopondin, and IGF2) was determined and used in combination with the expression values from the 13 genes for diagnosis of EOC.
  
  
  RESULTS
  Combined diagnostic models using either each five gene expression and plasma protein abundance values or 13 gene expression and six plasma protein abundance values can discriminate controls from patients with EOC with Receiver Operator Characteristics Area Under the Curve values of 0.998 and bootstrap .632+ validated classification errors of 3.1% and 2.8%, respectively. The sensitivities were 97.8% and 95.6%, respectively, at a set specificity of 99.6%.
  
  
  CONCLUSIONS
  The combination of gene expression and plasma protein based blood derived biomarkers in one diagnostic model increases the sensitivity and the specificity significantly. Such a diagnostic test may allow earlier diagnosis of epithelial ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Molecular Oncology Group, Medical University of Vienna, European Union, Vienna, Austria. dietmar.pils@univie.ac.at
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
authors.forename: Dan
authors.initials: D
authors.lastname: Tong
authors.forename: Gudrun
authors.initials: G
authors.lastname: Hager
authors.forename: Eva
authors.initials: E
authors.lastname: Obermayr
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.forename: Maria
authors.initials: M
authors.lastname: Kohl
authors.forename: Eva
authors.initials: E
authors.lastname: Schuster
authors.forename: Andrea
authors.initials: A
authors.lastname: Wolf
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Ioana
authors.initials: I
authors.lastname: Braicu
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
authors.forename: Paul
authors.initials: P
authors.lastname: Speiser
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000235:genetics*; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D003537:Cystadenoma / Q000097:blood* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000097:blood; D020738:Leptin / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D011388:Prolactin / Q000097:blood; D012372:ROC Curve; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D018394:CA-125 Antigen; C035170:IGF2 protein, human; D020738:Leptin; C451759:MUC16 protein, human; D008263:Macrophage Migration-Inhibitory Factors; D008565:Membrane Proteins; D053495:Osteopontin; D007335:Insulin-Like Growth Factor II; D011388:Prolactin; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
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