Biomarkers isolated from saliva successfully predict oral and breast cancer

Screening for breast cancer and the early detection of other tumors one day may be as simple as spitting into a collection tube or cup, according to recent studies by UCLA researchers.

In one early study based on a risk model, presented here at the 96th Annual Meeting of the American Association for Cancer Research, the UCLA scientists reported that genetic “biomarkers” isolated in saliva predicted oral squamous cell carcinoma in about nine out of 10 cases.

A recent study by this group, published in Clinical Cancer Research, disclosed similar predictive powers for head and neck cancers.

“These results indicate that such biomarkers found in saliva, called salivary transcriptomes, can be exploited for robust, high-throughput and reproducible tools for early disease detection,” said David T. Wong, professor and associate dean of research at the UCLA School of Dentistry and the Jonsson Comprehensive Cancer Center, the study’s senior investigator.

“This is a proof-of-principal study, but our results will need to be validated in a larger sample size in a blinded manner,” he added.

Also participating in the study were Yang Li, David Elashoff, MyungShin Oh, Stephanie Tsung, and Mai N. Brooks at UCLA.

Harvesting saliva and other bodily fluids for molecules that detect early cancers has long been a goal of scientists seeking quick and easy screening tools that could be done in a doctor’s office. The search for such tests, however, has been stalled until recently with the advance of several emerging technologies including improved methods to identify, collect, preserve and amplify genetic material and proteins.

In this study, the UCLA team found they could isolate messenger RNA from saliva and blood sera that might have diagnostic value for detecting early cancer. In the cell, messenger RNA or mRNA carries a copy of the genetic code or DNA, housed in the cell’s nucleus, to other parts of the cell for protein manufacture. The process by which genes are copied to mRNA, via an enzyme called RNA polymerase, is called transcription and the products are called transcripts.

The UCLA team collected saliva and blood from 32 patients with primary oral squamous cell carcinoma and 40 breast cancer patients, and matched each with saliva and blood from otherwise normal subjects. New techniques were developed to halt RNA degradation so the scientists could recover as much mRNA as possible for their samples. In all, the new techniques allowed the scientists to harvest up to 10,000 types of human mRNA from saliva, setting up a comparison test between cancer patients and the normal subjects based on analysis of their genetic “profiles.”

“Both serum and saliva exhibited unique genetic profiles,” said Wong. “The risk model yielded a predictive power of 95 percent by using only the salivary transcriptome samples and 88 percent by using only serum transcriptome samples for oral squamous cell carcinomas,” said Wong. “For oral cancer, salivary transcriptome has a slight edge of that of serum transcriptome analysis.”

Future research not only will involve a larger sample of cancer patients to refine prediction models, but also will include studies involving precancers and other difficult to detect cancers such as ovarian and pancreatic cancers.

“In my mind the biggest hurdle stems from the fact that salivary nucleic acids or protein markers might be influenced by eating, drinking, smoking, diet or oral hygiene,” said Wong. “So our goal is to provide the optimized and standardized protocol to assure consistent results.”

The studies are supported by grants from the U.S. Public Health Service (National Institute of Dental & Craniofacial Research) and the UCLA Jonsson Comprehensive Cancer Center to David T. Wong.