TAM pathway proteins as novel salivary biomarkers for periodontitis

Background: The identification of molecular biomarkers that help clinicians in early diagnosis is a key focus of periodontal research. The major aim of this cross-sectional observational study was to assess whether salivary TAM pathway protein levels have the potential to discriminate between periodontally healthy or gingivitis controls and periodontitis patients, including those with mild (I/II) or severe (III/IV) disease. Methods: Twenty-five periodontally healthy, 24 gingivitis, and 51 periodontitis patients further stratified into mild (stages I/II, n = 25) or severe (stages III/IV, n = 26) periodontitis were included. Salivary levels of tyrosine-protein kinase receptor UFO (AXL), TYRO3 protein tyrosine kinase (TYRO3), Proto-oncogene tyrosine-protein kinase MER (MERTK), and growth arrest-specific protein 6 (GAS6) were quantified using a multiplex immunoassay approach. Results: Salivary AXL, TYRO3, MERTK, and GAS6 levels were significantly elevated in periodontitis compared to periodontally healthy and gingivitis patients. Similar results for each periodontitis severity subgroup compared to control groups (except for MERTK, which was significantly different only for stage III/IV) were obtained. Supporting these findings, AXL, TYRO3, and GAS6 were the most accurate in differentiating between periodontally healthy/gingivitis and periodontitis, including mild or severe periodontitis (area under the curve [AUC] ranging from 0.72 to 0.89). Overall, combining biomarkers enhanced the predictive value for identifying periodontitis, including mild and severe disease, compared to using individual biomarkers alone (AUC values between 0.81 and 0.91). Conclusion: Salivary TAM pathway markers show promise as a potential noninvasive diagnostic screening tool to distinguish between controls (healthy/gingivitis) and periodontitis, including mild or severe periodontitis. Plain Language Summary: Salivary TAM pathway biomarkers can distinguish between periodontally healthy/gingivitis and periodontitis patients, including mild or severe periodontitis.