Using SWATH-MS to identify new molecular biomarkers in gingival crevicular fluid for detecting periodontitis and its response to treatment

J Clin Periodontol. 2024 Oct;51(10):1342-1358. doi: 10.1111/jcpe.14037. Epub 2024 Jul 10.

Abstract

Aim: To identify new biomarkers to detect untreated and treated periodontitis in gingival crevicular fluid (GCF) using sequential window acquisition of all theoretical mass spectra (SWATH-MS).

Materials and methods: GCF samples were collected from 44 periodontally healthy subjects and 40 with periodontitis (Stages III-IV). In the latter, 25 improved clinically 2 months after treatment. Samples were analysed using SWATH-MS, and proteins were identified by the UniProt human-specific database. The diagnostic capability of the proteins was determined with generalized additive models to distinguish the three clinical conditions.

Results: In the untreated periodontitis vs. periodontal health modelling, five proteins showed excellent or good bias-corrected (bc)-sensitivity/bc-specificity values of >80%. These were GAPDH, ZG16B, carbonic anhydrase 1, plasma protease inhibitor C1 and haemoglobin subunit beta. GAPDH with MMP-9, MMP-8, zinc-α-2-glycoprotein and neutrophil gelatinase-associated lipocalin and ZG16B with cornulin provided increased bc-sensitivity/bc-specificity of >95%. For distinguishing treated periodontitis vs. periodontal health, most of these proteins and their combinations revealed a predictive ability similar to previous modelling. No model obtained relevant results to differentiate between periodontitis conditions.

Conclusions: New single and dual GCF protein biomarkers showed outstanding results in discriminating untreated and treated periodontitis from periodontal health. Periodontitis conditions were indistinguishable. Future research must validate these findings.

Keywords: SWATH‐MS; diagnostic accuracy; molecular biomarkers; periodontitis; proteomics.

MeSH terms

  • Adult
  • Biomarkers* / analysis
  • Case-Control Studies
  • Dental Scaling
  • Female
  • Gingival Crevicular Fluid* / chemistry
  • Hemoglobins / analysis
  • Humans
  • Lipocalin-2 / analysis
  • Male
  • Mass Spectrometry
  • Matrix Metalloproteinase 8* / analysis
  • Matrix Metalloproteinase 9* / analysis
  • Middle Aged
  • Periodontitis* / diagnosis
  • Periodontitis* / metabolism
  • Periodontitis* / therapy
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Biomarkers
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9
  • MMP8 protein, human
  • Lipocalin-2
  • MMP9 protein, human
  • Hemoglobins