Validation and verification of predictive salivary biomarkers for oral health

Abstract

Oral health is important not only due to the diseases emerging in the oral cavity but also due to the direct relation to systemic health. Thus, early and accurate characterization of the oral health status is of utmost importance. There are several salivary biomarkers as candidates for gingivitis and periodontitis, which are major oral health threats, affecting the gums. These need to be verified and validated for their potential use as differentiators of health, gingivitis and periodontitis status, before they are translated to chair-side for diagnostics and personalized monitoring. We aimed to measure 10 candidates using high sensitivity ELISAs in a well-controlled cohort of 127 individuals from three groups: periodontitis (60), gingivitis (31) and healthy (36). The statistical approaches included univariate statistical tests, receiver operating characteristic curves (ROC) with the corresponding Area Under the Curve (AUC) and Classification and Regression Tree (CART) analysis. The main outcomes were that the combination of multiple biomarker assays, rather than the use of single ones, can offer a predictive accuracy of > 90% for gingivitis versus health groups; and 100% for periodontitis versus health and periodontitis versus gingivitis groups. Furthermore, ratios of biomarkers MMP-8, MMP-9 and TIMP-1 were also proven to be powerful differentiating values compared to the single biomarkers.

The Potential Impact of Salivary IL-1 on the Diagnosis of Periodontal Disease: A Pilot Study

“…Further studies should include many subjects and perform subgroup analysis according to age and systemic disease. In addition, a recent study [48] reported that a combination of multiple biomarkers rather than the use of single ones and the ratios of key biomarkers was important. A recent systematic review reported that the combination of MIP-1α, IL-1β, IL-6, and MMP-8 was acceptable as biomarkers for diagnosing periodontal disease [49].…”

Minimally Invasive Periodontology: A Treatment Philosophy and Suggested Approach

“…Indeed, the reliability of GCF in identifying cytokines is comparable to more invasive techniques such as gingival biopsies and blood serum, the latter being found to be the least sensitive [ 104 ]. It is likely necessary to employ holistic approaches in identifying multiple biomarkers in specific combinations for this purpose, rather than single or limited numbers of biomarkers [ 105 , 106 ]. For example, classification and regression tree analysis of a panel of salivary biomarkers including MMP-9, TIMP-1, and IL-1b was able to predict patients with periodontitis with an accuracy of close to 100% [ 106 ].…”

“…It is likely necessary to employ holistic approaches in identifying multiple biomarkers in specific combinations for this purpose, rather than single or limited numbers of biomarkers [ 105 , 106 ]. For example, classification and regression tree analysis of a panel of salivary biomarkers including MMP-9, TIMP-1, and IL-1b was able to predict patients with periodontitis with an accuracy of close to 100% [ 106 ]. The advent of high-throughput gene microarray analysis and large-scale proteomics may greatly contribute to the prediction and investigation of sites with disease activity, though this aspect remains largely unexplored [ 97 , 98 ], in part due to issues such as high costs and low recoverability of low-abundance cytokines [ 107 ].…”

Novel lab-on-a-disk platforms: a powerful tool for molecular fingerprinting of oral and respiratory tract infections

“…At the immunoassay level and for RTIs, the simultaneous detection of C-reactive protein (CRP) and/or procalcitonin (PCT) supports a more accurate prescription of antibiotic or antiviral treatments, especially if a NAAT result is negative but the symptoms indicate a bacterial/viral infection [17]. In oral diseases, host response biomarkers such as matrix metalloproteinases 8, 9 (MMP-8, MMP-9), tissue inhibitor of metalloproteinases (TIMP-1), hepatocyte growth factor (HGF) and others can differentiate between healthy, gingivitis and periodontitis disease states [18]. Bead-based immunoassays using fluorescent nanoparticles for detection can ensure multiplexing and render the immunoassay compatible with the TaqMan probe PCR detection during the integration in automated systems.…”