Screening Lung Adenocarcinoma Serum Autoantibody Marker

Introduction Recently, there is a growing tendency to search for tumor-associated autoantibodies as tumor markers. Since there are still no satisfying biomarkers for lung cancer and lung adenocarcinoma has increasing incidence in lung cancer, autoantibody signatures may be good candidate biomarkers.Methods A cDNA T7 phage-display library derived from ten lung adenocarcinoma tissues was constructed and tumor-associated antigens were enriched by 4 rounds of biopanning process. Through SEREX, positive phage clones were selected out. Arrayed positive phage clones were detected with 40 serum samples (26 from lung adenocarcinoma and 14 from healthy controls) and constructed a phage-clone diagnostic model. The clones in the model were sequenced and BLAST with GeneBank in NCBI. Subsequently, the phage-clone diagnostic model were validated by 193 serum samples (87 from lung adenocarcinoma, 77 from healthy controls and 29 from tuberculosis). The data was analyzed through discriminant analysis and leave-one-out cross validation were used to evaluate predictive accuracies of detectors. Other statistical analysis was performed.Results Approximately, a total of 22,000 single colonies were screened and picked 90 positive phage clones. A 19-phage-clone diagnostic model was constructed. Through validation process, several panels of autoantibody detectors were identified. One is a diagnostic autoantibody detector, the other is an autoantibody detector differentiating adenocarcinoma from healthy control and tuberculosis, another is an autoantibody detector differentiating adenocarcinoma from tuberculosis. Sensitivity and specificity of them are all higher than 80%. Among the diagnostic autoantibody detector, certain autoantibodies were related with sex, lymph node metastasis or T stage. When compare with CEA, sensitivity of the diagnostic autoantibody detector was higher than CEA and specificity was a little bit lower than CEA. There was no change in sensitivity and specificity raised a little when combination of CEA and the diagnostic autoantibody detector.Among the 19 phage peptides, there was no peptide streches derived from in-frame. 8 were shifted ORF, 2 was inserted reversely, 2 was out of CDS, 2 had no matched mRNA and 5 were predicted miscRNA.Conclusion In this study, lung adenocarcinoma associated antigens were screened by combining of T7 phage display and SEREX. Serum autoantibodies against tumor-associated antigens is very promising biomarkers for diagnosis and differentiation. The detector also can be used for screening lung adenocarcinoma.