Serum sCD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics

J Cell Mol Med. 2020 Nov;24(21):12537-12549. doi: 10.1111/jcmm.15796. Epub 2020 Sep 23.

Abstract

Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR-TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR-TB, a mass spectrometry strategy of data-independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR-TB group and the drug-sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR-TB. Our study has paved the way for a novel method to diagnose MDR-TB and may contribute to elucidate the mechanisms underlying MDR-TB.

Keywords: FGA; PGLYRP2; biomarker; data-independent acquisition; multidrug-resistant tuberculosis; parallel reaction monitoring; sCD14.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacterial Proteins / metabolism
  • Biomarkers / blood
  • Carrier Proteins / blood*
  • Female
  • Fibrinogen / metabolism*
  • Gene Ontology
  • Humans
  • Lipopolysaccharide Receptors / blood*
  • Male
  • Mass Spectrometry
  • Principal Component Analysis
  • Protein Interaction Maps
  • Proteomics*
  • Quality Control
  • ROC Curve
  • Tuberculosis, Multidrug-Resistant / blood*

Substances

  • Bacterial Proteins
  • Biomarkers
  • Carrier Proteins
  • FGA protein, human
  • Lipopolysaccharide Receptors
  • peptidoglycan recognition protein
  • Fibrinogen