Salivary diagnostics has come of age. In a mere six years, research supported by the National Institute of Dental and Craniofacial Research (NIDCR) has sprung to the forefront of basic, translational, and clinical research. In a scientific session on “Oral Fluid Diagnostics”, held during the 87th General Session of the International Association for Dental Research, at the Miami Beach Convention Center, researchers showcased a remarkable spectrum of research outcomes that expand the clinical applications of saliva based on ‘diagnostic toolboxes’, as well as establishing foundational mechanistic insights into salivary diagnostics.
Three papers highlighted the scientific and translational values of three diagnostic toolboxes (proteins, DNA, and RNA) in saliva. One research team identified 36 novel phosphoproteins in parotid saliva. This elegantly established the systemic phosphoproteome documentation technology, providing a powerful tool to evaluate health vs. disease states of oral and systemic disease. Another group explored the methylation status of genomic DNA contents of 807 cancer-associated genes in the saliva of oral cancer patients. Subpanels of these differentially methylated genes were able to discriminate oral cancer subjects with a specificity of 83-100% and a sensitivity of 62-77%, providing proof-of-concept data that differential methylation analysis of specific cellular genes in saliva can be used to detect oral cancer. A third diagnostic alphabet, the salivary transcriptome, was discovered to exist in saliva encapsulated in a lipid bilayer entity known as the exosome. This is a significant finding, since it provides the long-missing scientific rationale as to why endogenous salivary mRNA is unusually stable, firmly providing the scientific rationale for the translational utilization of the salivary transcriptome for biomarker studies.
This session also featured a paper that highlights a translational and clinical application of salivary biomarkers for detecting patients with acute coronary syndrome (ACS). Of interest is that discriminatory salivary biomarkers for ACS are gender- and fluid-specific (stimulated vs. unstimulated). The potential use of saliva, rather than blood, for ACS detection presents clear clinical advantages.
Last, there was a paper demonstrating the mechanistic insights into the value of salivary diagnostics for systemic disease detection. In rodent tumor transplantation models of melanoma and lung cancer, tumor-associative saliva biomarker profiles were observed. A systemic disease-induced salivary biomarker fingerprint is therefore validated. The working model proposed is that tumors, like endocrine organs, produce hormones, lymphokines, and cytokines, which will traverse through the vasculature and reach a distal organ to exert biological actions. When reaching the salivary glands, these hormones/lymphokines/cytokines will lead to transcriptional profile changes and ectopic protein translation, which will be secreted into saliva as tumor-associated surrogate biomarkers. This is the first mechanistic demonstration of a profile connection between systemic disease and salivary biomarkers.
Notes:
This is a summary of Sequence #52, “Oral Fluid Diagnostics”, presented during the 87th General Session of the International Association for Dental Research.
Contact: Linda Hemphill
International & American Association for Dental Research
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