A $200,000 grant from the Cancer Prevention and Research Institute of Texas will help the Baylor University Medical Center at Dallas launch a 3-year pilot study in using saliva to diagnose oral cancer. The metabolomics-based research will compare biomarker levels in the saliva of oral cancer patients, healthy volunteers, and those with oral inflammatory diseases.
“When people go to an oral hygienist, they often receive a thorough exam in the oral cavity to make sure there are no growths there,” said Teodoro Bottiglieri, PhD, director of the Center of Metabolomics at the Baylor Scott & White Health Institute of Metabolic Disease and a co-investigator on the study.
“But if they’re identifying them at that point, it’s already quite advanced,” said Bottiglieri. “You really don’t want to wait until that point, because the cancer can be aggressive.”
The researchers will focus on oral squamous cell carcinoma, which comprises more than 90% of oral cancers. Previous research has found more than 100 biomarkers that could indicate the disease, but those markers also are present in other common oral inflammatory diseases such as gum disease. This study would be the first to distinguish cancer from those problems, helping to prevent false positives.
“Almost all of the salivary biomarker research focuses on comparing the salivary components in cancer versus noncancerous patients or healthy controls,” said principal investigator Yi-Shing Lisa Cheng, DDS, MS, PhD, associate professor of diagnostic sciences at the Texas A&M University Baylor College of Dentistry.
“But they really haven’t expanded to individuals who have common oral inflammatory diseases but do not have cancer,” said Cheng. “Often, inflammation presents when cancer cells are present in the mouth, so we’re trying to find the biomarkers that could distinguish between the 2.”
Current salivary tests for oral cancer on the market rely on proteins or mRNAs. Bottiglieri and Cheng, however, are focusing on metabolites with small molecular weights. They believe that the salivary biomarkers that will come out of their approach may show higher specificity, which they say is a common weakness of most currently available diagnostic adjuncts for oral cancer.
In a targeted approach, the researchers will study a panel of specific metabolites and amino acids, including vitamin B9 folate, since women with low folate levels have shown an increased cancer risk. And in a secondary, untargeted approach, the researchers will perform a general analysis of more than 400 salivary metabolites from patients with oral cancer and from patients with common oral inflammatory diseases without cancer and then map these metabolites against a library of known compounds.
“If we find metabolic targets, it will be useful as a diagnostic test, but will also give us some information on which part of the metabolism is abnormal,” said Bottiglieri. “And that may lead to a potential target for treatment, so it’s a twofold purpose.”
The researchers say that promising results could lead to a saliva-based cancer test within the decade, but not before large-scale clinical research to validate the data. They also say that their studies may help in understanding the metabolic pathways that are altered in both oral cancer and gum disease, providing insight to develop potential treatments.
“This really is a pilot study,” said Bottiglieri. “And it will give us information on how best to go forward with a much larger study, because we can do a power analysis to see what the variability and data are like with these metabolites, since a lot of this methodology is very novel. But after a much larger trial, we’d be in a closer point where we would be able to say, ‘Yes, we have a good test.’”
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