MS-Based Crevicular Fluid Proteomics for the Study of Periodontal and Peri-Implant Conditions: A Systematic Review

This systematic review aimed to evaluate the current literature on mass spectrometry (MS)-based proteomic analysis of the crevicular fluid in different periodontal and peri-implant conditions, and to summarize methodological differences among studies. A search of electronic databases was conducted and clinical studies using MS-based proteomics in gingival (GCF) and/or peri-implant crevicular fluid (PICF) were considered for inclusion. The findings were synthesized and methodological variations described. A modified QUADOMICS tool was applied for risk of bias assessment. Thirteen studies; five longitudinal and eight cross-sectional were analyzed. Patients ranged from 10 to 190, with 42 to 3070 human proteins identified. Sample preparation and preanalytical procedures differed among studies. Protein identification, characterization and quantification were conducted using different algorithms and computer software against different databases. Different strategies were used to select distinctive proteins. Six studies attempted at biomarker development using different protein selection and validation criteria. While six studies presented moderate quality, seven were considered to be low quality. The present findings emphasize the need for methodological harmonization, including standardized protocols for GCF/PICF collection, harmonized proteomic workflows, multicenter longitudinal validation studies, and targeted mass spectrometry approaches for biomarker verification before they can be translated into the clinical practice.