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

Proteomics Clin Appl. 2020 Jan;14(1):e1900016. doi: 10.1002/prca.201900016. Epub 2019 Nov 18.

Abstract

Purpose: 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).

Experimental design: 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.

Results: 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%.

Conclusions: These findings indicate that these DSIgG Fc glycoforms are potential personalized biomarkers to differentiate NSCLC from BLDs.

Keywords: Fc glycopeptides; benign lung diseases; disease-specific IgG; non-small cell lung cancer; personalized biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Diagnosis, Differential*
  • Female
  • Humans
  • Immunoglobulin Fc Fragments / blood
  • Immunoglobulin G / blood
  • Lung Neoplasms / blood*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • glycosylated IgG