Disease-specific haptoglobin-β chain N-glycosylation as biomarker to differentiate non-small cell lung cancer from benign lung diseases

Background: The association of pathological states with N-glycosylation of haptoglobin-β has attracted increasing attention. Materials & Methods: In the present study, disease-specific haptoglobin-β (DSHp-β) was separated from serum immunoinflammation-related protein complexes (IIRPCs) of 600 participants including 300 patients with benign lung diseases (BLDs) and 300 patients with non-small cell lung cancer (NSCLC). The enriched glycopeptides of the tryptic digests of the DSHp-β were analyzed using matrix assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). Results: 20 of glycopeptides were detected for each sample. The statistical analysis has indicated that significant changes in the sialylation of DSHp-β between BLDs and NSCLC patients were observed. The age- and sex-matched participants were randomly clarified into the training set and the validation set. Receiver operating characteristic (ROC) analysis has revealed that the level ratio of glycopeptides (G2G3/G2G3S4) at the sites of Asn207/211 has potential capability to distinguish BLDs from NSCLC, with the sensitivity of 74.4%, the specificity of 82.8%, and the area under curve (AUC) of 0.805. Conclusion: The glycosylation of DSHp-β can distinguish NSCLC from BLDs with high diagnostic accuracy compared with current clinical available serum markers.