Evaluation of Salivary GAPDH as a Predictor Biomarker for Periodontitis

Periodontitis (PD) is a multifactorial, progressive inflammatory disease affecting the teeth-supporting tissues, characterized by an imbalance of the oral microbiota and the presence of bacterial biofilms leading to host response. Nowadays, reliable biochemical markers for early and objective diagnosis, and for predicting disease progression, are still lacking. Our previous proteomic investigations revealed the significant overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in periodontal pocket tissue, gingival crevicular fluid (GCF), and tooth-surface-collected material (TSCM) from PD patients in comparison to periodontally healthy controls, proposing it as a possible biomarker of PD. This study aimed to evaluate the expression of GAPDH in saliva, a more accessible, non-invasive, and clinically relevant oral sample. The whole saliva was analyzed by a preliminary mass spectrometry-based proteomic approach, identifying significantly increased levels of GAPDH also in salivary samples from periodontal-affected subjects. These data were further validated by enzyme-linked-immunosorbent assay (ELISA). Additionally, protein-protein interaction networks were generated through the Human Protein Atlas database, using different datasets (OpenCell, IntAct, and BioGRID). Bioinformatic analysis provided noteworthy GAPDH-associated networks potentially relevant to periodontal pathology. The scientific significance of this study lies in the detection of salivary GAPDH as a novel strategy to advance periodontal clinical diagnostics from the perspective of a non-invasive screening test. In correlation with other protein markers, salivary GAPDH could constitute a promising set of distinctive and predictive targets to enhance early diagnosis of PD, disease monitoring, and treatment planning in periodontology.