Research by scientists from the University of California, Los Angeles (UCLA) School of Dentistry could lead to a simple saliva test capable of diagnosing the early stages of oral cancer and diabetes, and perhaps neurological disorders and autoimmune diseases. Their findings are outlined in Clinical Chemistry (October 29, 2014).
The study, which is the most comprehensive analysis ever conducted of RNA molecules in human saliva, will also be published in the journal's January 2015 special issue, "Molecular Diagnostics: A Revolution in Progress."
Using state-of-the-science genomics and bioinformatics, the researchers analyzed 165 million genetic sequences and found that saliva contains many of the same disease-revealing molecules that are contained in blood.
Xinshu "Grace" Xiao, PhD, professor, department of integrative biology and physiology, and David Wong, DMD, DMSc, associate dean of research and a professor of oral biology at the University of California, Los Angeles School of Dentistry. Image courtesy of UCLA."If we can define the boundaries of molecular targets in saliva, then we can ask what the constituents in saliva are that can mark someone who has prediabetes or the early stages of oral cancer or pancreatic cancer -- and we can utilize this knowledge for personalized medicine," said senior study author David Wong, DMD, DMSc, in a statement. Dr. Wong is an associate dean of research and a professor of oral biology at the UCLA School of Dentistry and UCLA's Felix and Mildred Yip Endowed Professor in Dentistry.
The test also holds promise for diagnosing type 2 diabetes, gastric cancer, and other diseases, he said.
"If you don't look in saliva, you may miss important indicators of disease," Dr. Wong said. "There seems to be treasure in saliva, which will surprise people."
RNA, whose function as a cellular messenger that makes proteins and carries the instructions of DNA to other parts of a cell is well-established, is now understood to perform sophisticated chemical reactions and may also perform a number of other functions, at least some of which are unknown.
Dr. Wong's research has focused on identifying biomarkers in saliva. His laboratory discovered that some of the same RNA that is inside human cells is also present in saliva and can be used to detect diseases -- a surprising finding, he said, because enzymes in saliva can degrade RNA, making the mouth "a hostile environment."
While it was traditionally thought that RNA may only have a linear form, recent research identified a circular form of RNA. The UCLA scientists have identified more than 400 circular RNA in human saliva, including 327 forms of RNA that were previously undiscovered. The function of this circular RNA in saliva is not yet understood. The researchers noted that it does serve as a sponge for tiny microRNAs, which bind to it.
"Circular RNAs in saliva may be protecting other RNAs," said Xinshu "Grace" Xiao, PhD, a UCLA associate professor of integrative biology and physiology. Circular RNAs in saliva likely protect microRNAs from being degraded, she said.
MicroRNAs play important roles in many cell types and have been implicated in cancers and other diseases, Xiao said. Once considered to be little more than molecular noise, one microRNA can regulate hundreds of genes.
In the study, the authors compared microRNA levels in saliva to those in the blood and other body fluids. They discovered that the levels of microRNA in blood and saliva are very similar -- meaning that a saliva sample would be a good measure of microRNAs in the body.
Piwi-interacting RNAs, or piRNAs, also were found in saliva. These are a class of small RNAs produced by stem cells, skin cells, and germ cells. Very few piRNAs are in blood and most other body fluids, but Xiao's analysis showed that piRNAs are abundant in saliva. Although their function is not yet known, they may protect the body from viral infection, Xiao said.
Another class of RNA is noncoding RNA, which does not translate genetic code from DNA to make proteins.
"Saliva carries with it noncoding RNAs, microRNAs, piRNAs, and circRNAs that are biomarkers for disease and health monitoring," Dr. Wong said. "Had we not done this collaboration, we would never know that noncoding RNAs, microRNAs, piRNAs, and circRNAs exist in saliva."
The authors speculated that dentists might be able to take saliva samples to analyze for a variety of diseases soon. The research could lead to a new category of self-diagnostic devices, according to Dr. Wong.
"This could indicate that wearable gear that informs you whether you have a disease -- even before you have any symptoms -- is almost here," he said.
The research was supported by the National Institute of Health's National Center for Advancing Translational Sciences.
