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

ABSTRACT: Background: The association of pathological states with N-glycosylation of haptoglobin-? has attracted increasing attention. Materials & Methods: In the present study, disease-specific haptoglobin-? (DSHp-?) 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-? 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-? 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-? can distinguish NSCLC from BLDs with high diagnostic accuracy compared with current clinical available serum markers.

SUBMITTER: Chen T

PROVIDER: S-EPMC6843889 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Chen Tianjing T He Chengyan C Zhang Mo M Li Xiaoou X Liu Xiaofeng X Liu Yujie Y Zhang Dan D Li Zhili Z

Journal of Cancer 20190907 23

<b>Background</b>: The association of pathological states with N-glycosylation of haptoglobin-β has attracted increasing attention. <b>Materials & Methods</b>: 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 w ...[more]

PMID: 31737099

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Project description:Haptoglobin (Hp) is a glycoprotein that binds free hemoglobin (Hb) in plasma and plays a critical role in tissue protection and prevention of oxidative damage. Besides, it has some regulatory functions. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. The human Нр gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of haptoglobin: homozygous Нр1-1 and Нр2-2, and heterozygous Нр2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual predisposition of a person to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting off the Pre-Hp precursor molecule into two subunits, α and β, limited proteolysis of α-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of α-chains and glycosylation of the β-chain. Glycosylation of the β-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the β-chain of Hp has become the main direction in the study of pathological processes, including malignant neoplasms. These characteristics indicate the possibility of the existence of Hp in the form of a multitude of proteoforms, probably performing different functions. This review is devoted to the description of the structural and functional diversity and the potential use of Hp as a biomarker of various pathologies.

Project description:BackgroundPulmonary imaging often identifies suspicious abnormalities resulting in supplementary diagnostic procedures. This study aims to investigate whether the metabolic fingerprint of plasma allows to discriminate between patients with lung inflammation and patients with lung cancer.MethodsMetabolic profiles of plasma from 347 controls, 269 cancer patients and 108 patients with inflammation were obtained by 1H-NMR spectroscopy. Models to discriminate between groups were trained by PLS-LDA. A test set was used for independent validation. A ROC curve was built to evaluate the diagnostic performance of potential biomarkers.ResultsSensitivity, specificity, PPV and NPV of PET-CT to diagnose cancer are 96, 23, 76 and 71%. Metabolic profiles differentiate between cancer and inflammation with a sensitivity of 89%, a specificity of 87% and a MCE of 12%. Removal of the glutamate metabolite results in an increase of MCE (38%) and a decrease of both sensitivity and specificity (62%), demonstrating the importance of glutamate for discrimination. At the cut-off point 0.31 on the ROC curve, the relative glutamate concentration discriminates between cancer and inflammation with a sensitivity of 85%, a specificity of 81%, and an AUC of 0.88. PPV and NPV are 92 and 69%. In PET-positive patients with a relative glutamate level???0.31 the sensitivity to diagnose cancer reaches 100% with a PPV of 94%. In PET-negative patients, a relative glutamate level?>?0.31 increases the specificity of PET from 23% to 58% and results in a high NPV of 100%. In case of discrepancy between SUVmax and the glutamate concentration, lung cancer is missed in 19% of the cases.ConclusionThis study indicates that the 1H-NMR-derived relative plasma concentration of glutamate allows discrimination between lung cancer and lung inflammation. A glutamate level???0.31 in PET-positive patients corresponds to the diagnosis of lung cancer with a higher specificity and PPV than PET-CT. Glutamate levels >?0.31 in patients with PET negative lung lesions is likely to correspond with inflammation. Caution is needed for patients with conflicting SUVmax values and glutamate concentrations. Confirmation is needed in a prospective study with external validation and by another analytical technique such as HPLC-MS.

Dataset Information

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

Publications

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

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