Proteomics for the discovery of biomarkers and diagnosis of periodontitis: a critical review

Abstract

Periodontitis is a common chronic and destructive disease whose pathogenetic mechanisms remain unclear. Due to their sensitivity and global scale, proteomics studies offer the opportunity to uncover critical host and pathogen activity indicators and can elucidate clinically applicable biomarkers for improved diagnosis and treatment of the disease. This review summarizes the literature of proteomics studies on periodontitis and comprehensively discusses commonly found candidate biomarkers. Key considerations in the design of an experimental proteomics platform are also outlined. The applicability of protein biomarkers across the progression of periodontitis and unexplored areas of research are highlighted.

Keywords::

• 2D gel electrophoresis
• aggressive periodontitis
• biomarkers
• chronic periodontitis
• gingivitis
• gingival crevicular fluid
• shotgun proteomics
• whole saliva

Financial & competing interests disclosure

CA Floudas acknowledges financial support from the National Science Foundation (CBET-0941143) and the National Institute of Health (R01LM009338). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Periodontitis is a common, chronic and destructive disease that affects individual as well as public health costs. The pathogenetic mechanisms of periodontitis are not well understood.

• The correlation of periodontitis as a risk factor for various systemic conditions has been extensively investigated, rendering the search for biomarkers of periodontitis extremely useful. Protein biomarkers can be applied in practice to many phases of periodontitis, from disease onset to clinical endpoint.

• The literature contains a limited number of differential proteomics studies on periodontitis. These studies have outlined a number of candidate protein biomarkers correlated with periodontal disease or health, summarized in Table 2, including actin-binding proteins, plasma proteins, lipoprotein components, antimicrobial peptides and catalytic enzymes.

• Gingival crevicular fluid as a sample medium is highly disease-specific, but its collection remains technically demanding. Collection of whole saliva is rapid and nontechnical, but analyses are complicated by changes in composition, glandular contributions and protein abundance ranges.

• Utilization of two-dimensional electrophoresis as the driver of proteomics studies remains the primary choice for straightforward quantification and identification of protein isoforms. High-throughput bottom-up proteomics platforms greatly increase the number of identifications made and have risen in prominence, but quantification requires more advanced methods and the vast amounts of data produced must be processed robustly.

• Advanced algorithms for the selection of small biomarker subsets from vast datasets have been applied to proteomics studies of periodontitis with success, and will continue to be developed.

• Certain areas that would benefit from the discovery and application of biomarkers, such as prediction or determination of disease onset or temporal disease stage indicators, remain unexplored by large-scale proteomics studies. Pooled and site-specific analyses can greatly contribute to the investigation of dynamic changes of the proteome after treatment and in responding versus non-responding sites.