Salivary microRNA (miRNA) could provide a noninvasive way to detect oral squamous cell carcinoma (OSCC) and perhaps monitor the disease's development in oral lichen planus patients, according to a new study in the Journal of Dental Research (July 2014, Vol. 93:7, pp. 86S-93S).
Oral cancer -- of which more than 90% is OSCC -- is one of the most prevalent cancers worldwide. Over the years, diagnosis and management of OSCC patients has improved through new treatment modalities in surgery, radiotherapy, and chemotherapy, but the overall five-year survival rate remains around 62%.
Late diagnosis, recurrences, and frequent regional lymph-node metastasis are the major causes for the poor prognosis. Currently, OSCC detection depends on a clinical examination of the oral cavity, followed by histologic evaluation of suspected lesions, which are likely to be undetectable in hidden sites. Accordingly, clinically effective biomarkers for the early detection of OSCC could greatly improve the survival rate and prognosis, noted lead author Fatemeh Momen-Heravi, from University of Massachusetts Medical School, and colleagues.
Recently, the detection of microRNA biomarkers in different biofluids, including plasma, serum, and saliva, has introduced a new paradigm in biomarker discovery. The miRNAs are endogenous, small, noncoding, regulatory RNAs that negatively regulate gene expression at the translational level by base pairing to the 3'-untranslated region of target messenger RNA. It is estimated that nearly a third to a half of human genes are regulated by miRNAs, and each miRNA is predicted to target several hundred transcripts, making miRNAs one of the extensive classes of gene regulators.
Salivary miRNA biomarkers have become an emerging field for monitoring oral and systemic diseases. In carcinogenesis, overexpression of certain miRNAs could result in downregulation of tumor suppressor genes, while underexpression of certain miRNAs could cause oncogene upregulation. This indicates that miRNAs may play a role as either tumor suppressors or oncogenes.
Therefore, salivary miRNA screening emerges as a novel diagnostic method for detecting human cancers, especially at early stages, according to the researchers.
However, a lack of well-characterized or matched clinical groups and a lack of suitable endogenous controls (ECs) for salivary miRNA detection and normalization are among the restrictions of applying salivary-based miRNA biomarker discovery, they wrote.
In this study, Momen-Heravi and colleagues examined the differential expression pattern of miRNAs among four groups of subjects -- patients with OSCC, those with OSCC in remission (OSCC-R), patients with oral lichen planus (OLP), and healthy controls (HCs) -- using a genomewide high-throughput miRNA microarray.
Patients with OLP have been found to have a higher risk for developing OSCC, although whether OLP is premalignant is still a controversial issue, the researchers wrote.
Results
The study included saliva samples from 34 patients at the Stomatology Center at Texas A&M Baylor College of Dentistry, from April 2010 through September 2011. This included nine OSCC patients before treatment, eight patients with OSCC-R, eight patients with OLP, and nine healthy controls. There was no significant difference among the mean ages of the different study groups (p > 0.05).
The researchers first screened samples for identifying a stable EC in miRNA profiling data. Human viral miRNAs are virus encoded and can be expressed in humans as a result of previously integrated viral genome.
The researchers identified miRNA-27b, which showed significantly higher levels in the OSCC patients than in the healthy controls, the OSCC-R patients, and the OLP patients.
"Our results suggest that a significantly elevated level of miRNA-27b is an indicator of OSCC presence," the researchers wrote. "Therefore, miRNA-27b could be a promising candidate for salivary-based OSCC detection."
In contrast to the findings in the saliva of OSCC patients, reduced levels of miRNA-27b have been reported in the cancer tissues and plasma of these patients, the researchers pointed out. The different miRNA-27b levels in saliva and tissue could be related to the dual activity of miRNA-27b in tumor initiation and progression.
"Consequently, OSCC cells may selectively release miRNA-27b into saliva, and this phenomenon results in significantly elevated salivary miRNA-27b levels," they wrote.
The study also showed that underexpression of miRNA-136 can distinguish OSCC patients from those with OSCC-R and healthy controls.
The researchers also identified miRNA-191 as a stable EC for normalization of salivary miRNA data and found that miRNA profiles in the OSCC patients, patients with OSCC-R, OLP patients, and healthy controls were distinctively different.
"These findings suggest that miRNA-191 could be considered a suitable EC for salivary miRNA biomarker studies," they wrote.
"Our novel findings suggest that salivary miRNA expression profiles could be used as a noninvasive method for detecting OSCC and perhaps for monitoring OSCC development in OLP patients," the researchers concluded.
