J Cancer 2019; 10(23):5628-5637. doi:10.7150/jca.32690

Research Paper

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

Tianjing Chen1, Chengyan He2, Mo Zhang1, Xiaoou Li3, Xiaofeng Liu3, Yujie Liu1, Dan Zhang1, Zhili Li1,✉

1. Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, PR China
2. Clinical Lab Diagnosis, China-Japan Union Hospital, Jilin University, Changchun, PR China
3. Department of Laboratory, Tumor Hospital of Jilin Province, Changchun, PR China

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Chen T, He C, Zhang M, Li X, Liu X, Liu Y, Zhang D, Li Z. Disease-specific haptoglobin-β chain N-glycosylation as biomarker to differentiate non-small cell lung cancer from benign lung diseases. J Cancer 2019; 10(23):5628-5637. doi:10.7150/jca.32690. Available from http://www.jcancer.org/v10p5628.htm

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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.

Keywords: disease-specific haptoglobin β chain, glycosylation, lung diseases, pathological state, matrix assisted laser desorption/ionization-mass spectrometry.