title: Performance of a multiplexed dual analyte immunoassay for the early detection of non-small cell lung cancer.
abstract: OBJECTIVE
  "PAULA's" test (Protein Assays Utilizing Lung cancer Analytes) is a novel multiplex immunoassay blood test that incorporates both tumor antigens and autoantibodies to determine the risk that lung cancer (LC) is present in individuals from a high-risk population. The test's performance characteristics were evaluated in a study using 380 retrospective clinical serum samples.
  
  
  METHODS
  PAULA's test is performed on the Luminex xMAP technology platform, and detects a panel of 3 tumor antigens (CEA, CA-125, and CYFRA 21-1) and 1 autoantibody marker (NY-ESO-1). A training set (n = 230) consisting of 115 confirmed diagnoses of non-small cell lung carcinoma (NSCLC) cases and 115 age- and smoking history-matched controls was used to develop the LC predictive model. Data from an independent matched validation set (n = 150) was then used to evaluate the model developed, and determine the ability of the test to distinguish NSCLC cases from controls.
  
  
  RESULTS
  The 4-biomarker panel was able to discriminate NSCLC cases from controls with 74% sensitivity, 80% specificity, and 0.81 AUC in the training set and with 77% sensitivity, 80% specificity, and 0.85 AUC in the independent validation set. The use of NY-ESO-1 autoantibodies substantially increased the overall sensitivity of NSCLC detection as compared to the 3 tumor markers alone. Overall, the multiplexed 4-biomarker panel assay demonstrated comparable performance to a previously employed 8-biomarker non-multiplexed assay.
  
  
  CONCLUSIONS
  These studies confirm the value of using a mixed panel of tumor antigens and autoantibodies in the early detection of NSCLC in high-risk individuals. The results demonstrate that the performance of PAULA's test makes it suitable for use as an aid to determine which high-risk patients need to be directed to appropriate noninvasive diagnostic follow-up testing, especially low-dose CT (LDCT).
authors.affiliation: 20/20 GeneSystems, 9430 Key West Avenue, Rockville, MD, 20850, USA. vdoseeva@2020gene.com.
authors.forename: Victoria
authors.initials: V
authors.lastname: Doseeva
authors.affiliation: Abbott Molecular Inc, 1300 E Touhy Avenue, Des Plaines, IL, 60018, USA. Tracey.Colpitts@abbott.com.
authors.forename: Tracey
authors.initials: T
authors.lastname: Colpitts
authors.affiliation: 20/20 GeneSystems, 9430 Key West Avenue, Rockville, MD, 20850, USA. yanshangao@gmail.com.
authors.forename: Grace
authors.initials: G
authors.lastname: Gao
authors.affiliation: 20/20 GeneSystems, 9430 Key West Avenue, Rockville, MD, 20850, USA. jwoodcock@2020gene.com.
authors.forename: Juliana
authors.initials: J
authors.lastname: Woodcock
authors.affiliation: 20/20 GeneSystems, 9430 Key West Avenue, Rockville, MD, 20850, USA. vknezevic@2020gene.com.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Knezevic
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D016022:Case-Control Studies; D003710:Demography; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor