title: Lung cancer-associated auto-antibodies measured using seven amino acid peptides in a diagnostic blood test for lung cancer.
abstract: Autoantibody profiling is a developing approach that incorporates immune recognition of myriad aberrant cancer proteins into a single diagnostic assay. We have previously described methodology to screen T7-phage NSCLC-cDNA libraries for phage-expressed proteins recognized by NSCLC-associated antibodies, and developed a multiplex assay that has excellent ability to discriminate NSCLC from control samples. This follow-up report describes the development and testing of a diagnostic autoantibody assay that uses seven amino-acid peptides as capture proteins. A random-peptide M13-phage library was screened for proteins recognized by cancer-associated antibodies. One hundred twenty-one NSCLC case and control samples were divided into two groups for training and validation, or alternately, evaluated sequentially in a leave-one-out analysis. Candidate antibody-markers were ranked by statistical discrimination between cases and controls. Receiver-Operating-Characteristic (ROC-AUC) suggested the predictive potential of various marker combinations. A five-marker combination (AUC = 0.982) afforded 90% sensitivity and 73% specificity in a training-and-testing strategy. Leave-one-out validation provided similar class prediction. Data confirm the potential of antibody profiling to provide high levels of cancer prediction. Random peptide libraries offer a universal source of capture proteins for antibody profiling that obviates the need for tumor-specific library construction and abrogates inherent problems with tumor heterogeneity during biomarker discovery.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Lexington, KY, USA.
authors.forename: Nada H
authors.initials: NH
authors.lastname: Khattar
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Coe-Atkinson
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Stromberg
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
authors.forename: Edward A
authors.initials: EA
authors.lastname: Hirschowitz
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology*; D008297:Male; D019151:Peptide Library; D017422:Sequence Analysis, DNA
chemical_list: D000596:Amino Acids; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D019151:Peptide Library