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FEATURE ARTICLE

Salivary Diagnostics

Amazing as it might seem, doctors can detect and monitor diseases using molecules found in a sample of spit

David T. Wong

Next Steps

In addition to our investigations of oral cancer, my research team and our collaborators have worked to identify salivary biomarkers for several other diseases. Most recently, we published a paper on a group of 26 RNA biomarkers that characterize Sjögren's syndrome, which primarily affects the salivary glands and tear ducts but can also cause symptoms in many other tissues. Although it is not well known, Sjögren's syndrome is a common condition, affecting between 1,000,000 and 4,000,000 million people, predominantly women, in the United States. The wide range of this estimated prevalence reflects the difficulty of identifying this condition. As with many autoimmune diseases, symptomatic episodes come and go, varying in duration and severity. The Sjögren's Syndrome Foundation reports that the average patient experiences a lag of six years between the onset of symptoms and diagnosis.

Figure%207.%20Click to Enlarge ImageMy colleagues and I have also focused considerable effort on finding RNA signatures for major diseases that affect parts of the body other than the mouth. Although we have not published these results, our preliminary studies identified a group of RNA biomarkers that appear to characterize breast cancer. We've also found evidence that salivary biomarkers may support the diagnosis of type-II diabetes and pancreatic cancer. However, it is important to note that these studies are ongoing.

Another forward-looking project that we are excited about is a collaboration with Chih-Ming Ho in the School of Engineering at UCLA. Our colleagues there have developed so-called "micro- and nano-electrical-mechanical-system" biosensors—tiny, self-contained machines that automate the process of detecting extremely small quantities of target molecules. Within a few years, we hope to have prototypes for a handheld device that would enable an investigator or clinician to detect proteins or RNAs in a sample of saliva without having to resort to a roomful of instruments.

Before this device or any other ambitious application of salivary diagnostics can become a reality, the field as a whole must make significant strides. At present, few salivary biomarkers of disease exist, although we believe that we have promising early evidence that saliva can be used to detect breast cancer, pancreatic cancer and type-II diabetes. But as the field of biomarker diagnosis grows, such molecular signatures may prove to be just the tip of the iceberg—especially if one considers what can also be gleaned from other materials, such as blood, urine, spinal fluid, tears, nipple aspirate or feces. It seems likely that biomarkers for certain diseases will prove to be more abundant in some types of samples than in others. Which works best for what? That question will undoubtedly remain under investigation in coming years. However, my colleagues and I remain optimistic that saliva will continue to reveal secrets about the state of disease or health in both the mouth and the rest of the body. All from lowly spit! We consider it a blessing.

Bibliography

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  • Herr, A. E., A. V. Hatch, D. J. Throckmorton, H. M. Tran, J. S. Brennan, W. V. Giannobile and A. K. Singh. 2007. Microfluidic immunoassays as rapid saliva-based clinical diagnostics. Proceedings of the National Academy of Sciences of the U.S.A. 104:5268-5273.
  • Hu, S., Y. Li, J. Wang, Y. Xie, K. Tjon, L. Wolinsky, R. R. Loo, J. A. Loo and D. T. Wong. 2006. Human saliva proteome and transcriptome. Journal of Dental Research 85:1129-1133.
  • Hu, S., Y. Xie, P. Ramachandran, R. R. Ogorzalek Loo, Y. Li, J. A. Loo and D. T. Wong. 2005. Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry. Proteomics 5:1714-1728.
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  • Hu, S., T. Yu, Y. Xie, Y. Yang, Y. Li, X. Zhou, S. Tsung, R. R. Loo, J. R. Loo and D. T. Wong. 2007. Discovery of oral fluid biomarkers for human oral cancer by mass spectrometry. Cancer Genomics & Proteomics 4:55-64.
  • Li, Y., M. A. St. John, X. Zhou, Y. Kim, U. Sinha, R. C. Jordan, D. Eisele, E. Abemayor, D. Elashoff, N. H. Park and D. T. Wong. 2004. Salivary transcriptome diagnostics for oral cancer detection. Clinical Cancer Research 10:8442-8450.
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  • Vigneswaran, N., D. C. Baucum, J. Wu, Y. Lou, J. Bouquot, S. Muller and W. Zacharias. 2007. Repression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not its receptors during oral cancer progression. BioMedCentral Cancer 7:108.



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