Autoantibody Signatures Discovered by HuProt Protein Microarray to Enhance the Diagnosis of Lung Cancer
Abstract Background: This study aims to comprehensively discover novel autoantibodies (TAAbs) against tumor-associated antigens (TAAs) and establish diagnostic models for assisting in the diagnosis of lung cancer (LC) and discrimination of pulmonary nodules (PN).Methods: HuProt human microarray was used to discover the candidate TAAs and Enzyme-linked immunosorbent assay (ELISA) was performed to detect the level of TAAbs in 634 participants of two independent validation cohorts. Logistic regression analysis was used to construct models. Receiver operating characteristic curve (ROC) analysis was utilized to assess the diagnostic value of models.Results: Eleven TAAs were discovered by means of protein microarray and data analysis. The level of ten TAAbs (anti-SARS, anti-ZPR1, anti-FAM131A, anti-GGA3, anti-PRKCZ, anti-HDAC1, anti-GOLPH3, anti-NSG1, anti-CD84 and anti-EEA1) was higher in LC patients than that in NC of validation cohort 1 (P<0.05). The model 1 comprising 4 TAAbs (anti-ZPR1, anti-PRKCZ, anti-NSG1 and anti-CD84) and CEA reached an AUC of 0.813 (95%CI: 0.762-0.864) for diagnosing LC from normal individuals. 5 of 10 TAAbs (anti-SARS, anti-GOLPH3, anti-NSG1, anti-CD84 and anti-EEA1) existed a significant difference between malignant pulmonary nodules (MPN) and benign pulmonary nodules (BPN) patients in validation cohort 2 (P<0.05). Model 2 consisting of anti-EEA1, traditional biomarkers (CEA, CYFRA211 and CA125) and 3 CT characteristics (vascular notch sign, lobulation sign, mediastinal lymph node enlargement) could distinguish MPN from BPN patients with an AUC of 0.845 (sensitivity: 58.3%, specificity: 96.6%).Conclusions: High-throughput protein microarray is an efficient approach to discovering novel TAAbs which could increase the accuracy of lung cancer diagnosis in the clinic.