Disease‐Specific IgG Fc Glycosylation Ratios as Personalized Biomarkers to Differentiate Non‐Small Cell Lung Cancer from Benign Lung Diseases

Abstract

The authors aimed to separate Fc N-glycopeptides of disease-specific immunoglobulin G (DSIgG) as personalized biomarkers to distinguish non-small cell lung cancer (NSCLC) from benign lung diseases (BLDs). DSIgG from 509 BLDs patients and 477 NSCLC patients was isolated using native polyacrylamide gel electrophoresis and then the Fc glycosylation was determined using mass spectrometry. For the patients below 60 years of age, a combination of the glycopeptides ratios with one fucose residue difference of DSIgG1 and DSIgG2 can differentiate NSCLC from BLDs, with area under curve (AUC) values of >0.76, sensitivities of >87%, and specificities of >61%. For the patients above 60 years of age, a combination of the glycopeptides ratios with one monosaccharide residue of DSIgG2 can differentiate NSCLC from BLDs, with AUC values of >0.78, sensitivities of >91%, and specificities of >54%. For the same participants, the commonly used clinical biomarkers have AUC values of 0.5-0.621, sensitivities of 15.8-32.9%, and specificities of 75.7-90.5%. These findings indicate that these DSIgG Fc glycoforms are potential personalized biomarkers to differentiate NSCLC from BLDs.