Autoantibodies against specific lung cancer-associated antigens have been suggested for the performance of lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of the antigen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, neutrophil gelatinase-associated lipocalin (NGAL), and neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9-guanine DNA chip method. The ratios of AICs to their antigens and the combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than those for their free antigens in all participants. The levels of each free antigens distinguished patients with NSCLC from the HCs. The ratios of the AIC to its antigen and seven combinations of two to four ratios were significantly higher in patients with NSCLC than in the HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at a 3.51 cut-off. Higher sensitivity was observed in the early stages (0-I) and adenocarcinoma than in stages II-IV and other pathological types. Combining all ratios of AICs and their antigens for all four markers was useful when diagnosing NSCLC.
